Methods and apparatus for imaging discrete wavelength bands using a mobile device

ABSTRACT

An attachment device comprising a cover, with first and second windows, is affixed to a backing, with third and fourth windows, thereby forming a casing. The first and third windows form a first optical path with light entering the third window passing through the first window. The second and fourth windows form a second optical path with light entering the second window passing through the fourth window. A filter housing with a plurality of filters is driven by a motor so that the filters intercept the first optical path in accordance with an imaging regimen electronically stored in the casing interior. The imaging regimen communicates instructions, via a communications interface of the attachment device, to an imager and light source of an external device, to which the attachment device is attached, thereby controlling these components in accordance with the regimen.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/222,006, filed Sep. 22, 2015, the disclosure of which is herebyincorporated by reference herein in its entirety for all purposes.

FIELD OF THE APPLICATION

This application generally relates to systems and methods forhyperspectral/multispectral imaging.

BACKGROUND

Hyperspectral/multispectral spectroscopy is an imaging technique thatintegrates multiples images of an object resolved at different narrowspectral bands (e.g., narrow ranges of wavelengths) into a single datacube, referred to as a hyperspectral/multispectral data cube. Dataprovided by hyperspectral/multispectral spectroscopy allow for theidentification of individual components of a complex composition throughthe recognition of hyperspectral/multispectral signatures for individualcomponents within the hyperspectral/multispectral data cube.

Hyperspectral/multispectral spectroscopy has been used for a variety ofapplications, ranging from geological and agricultural surveying tomilitary surveillance and industrial evaluation. For example, satellitehyperspectral/multispectral imaging has been used in mineralexploration, environmental monitoring and military surveillance. (See,Bowles J. H. et al., Imaging Spectrometry III; 1997: Proc SPIE 1997. p.38-45; Riaza A. et al., Inteml J Applied Earth Observation andGeoinformation Special issue: Applications of imaging spectroscopy 2001;3-4:345-354; Thenkabail P. S. et al., Remote Sens Environ 2000; 71(REMOTE SENS ENVIRON):158-182; and Tran C. D., Fresenius J Anal Chem2001; 369(3-4):313-9, the contents of which are hereby incorporatedherein by reference in their entireties for all purposes.)

Hyperspectral/multispectral spectroscopy has also been used in medicalapplications to assist with complex diagnosis and predict treatmentoutcomes. For example, medical hyperspectral/multispectral imaging hasbeen used to accurately predict viability and survival of tissuedeprived of adequate perfusion, and to differentiate diseased (e.g.tumor) and ischemic tissue from normal tissue. (See, Colarusso P. etal., Appl Spectrosc 1998; 52:106A-120A; Greenman R. I. et al., Lancet2005; 366:1711-1718; and Zuzak K. J. et al., Circulation 2001;104(24):2905-10; the contents of which are hereby incorporated herein byreference in their entireties for all purposes.)

Despite the great potential hyperspectral/multispectral spectroscopyholds for medical imaging, several drawbacks have limited its use in theclinic setting (Kester R. T. et al., J. Biomed. Opt. 16, 056005 (May 10,2011)). For example, medical hyperspectral/multispectral instruments arecostly, typically tens to hundreds of thousands of dollars, due to thecomplex optics required to resolve images at a plurality of narrowspectral bands. The cost and inconvenience of usinghyperspectral/multispectral imaging for routine screening and/ormonitoring of medical conditions is further increased by the requirementthat subjects visit a clinical environment with ahyperspectral/multispectral imaging device. This incurs administrativecosts, medical professional service costs, and further clogs theclinical environment.

Thus, there is an unmet need in the field for less expensive and morerapid means of hyperspectral/multispectral imaging. The presentdisclosure meets these and other needs by providing devices, methods,and systems for performing hyperspectral/multispectral imaging withexternal devices.

SUMMARY

The present disclosure addresses the above-identified shortcomings byproviding an attachment device that attaches to an external device. Theexternal device can be, for example, a smart phone, a personal digitalassistant (PDA), an enterprise digital assistant, a tablet computer, ora digital camera. In a typical embodiments, the attachment deviceattaches (e.g., clips or screws on) to the external device. In oneembodiment, the external device is a smart phone and the attachmentdevice clips onto the smart phone. The attachment device is aself-contained casing in its own right. In one embodiment theself-contained casing of the attachment device comprises a cover that isaffixed to a backing. The cover has first and second windows while thebacking has matching third and fourth windows in the sense that thefirst and third windows form a first optical path with light enteringthe third window passing through the first window while the second andfourth windows form a second optical path with light entering the secondwindow passing through the fourth window. Inside the casing of theattachment device there is a movable filter housing. The movable filterhousing has a plurality of filters and movement of the filter housing isdriven by a motor. In this way, the filters of the filter housingselectively intercept the first optical path in accordance with animaging regimen electronically stored in the casing interior. Theimaging regimen communicates instructions, via a communicationsinterface of the attachment device, to an imager and light source of anexternal device, to which the attachment device is attached, therebycontrolling these components in accordance with the regimen.

Now that an overview of the present disclosure has been provided,specific detailed embodiments are provided.

Attachment Embodiments

One such embodiment provides an attachment device comprising a cover,having a first optical window and a second optical window, and abacking, having a third optical window and a fourth optical window. Thecover is affixed onto the backing thereby forming a casing having aninterior. The first and third optical window form a first optical pathwithin the casing interior, in which light entering the third opticalwindow passes through the first optical window. The second and fourthoptical window form a second optical path within the casing interior, inwhich light entering the second optical window passes through the fourthoptical window. A filter housing, in the interior of the casing,comprises a plurality of filters. Each filter in the plurality offilters characterized by a wavelength range in a plurality of wavelengthranges. The filter housing is movable along or about an axis to therebyselectively intercept the first optical path. A first filter in theplurality of filters is characterized by a first wavelength range in theplurality of wavelength ranges. The first filter is transparent to thefirst wavelength range and opaque to other wavelengths in at least thevisible spectrum. A second filter in the plurality of filters ischaracterized by a second wavelength range in the plurality ofwavelength ranges, where the second filter is transparent to the secondwavelength range and opaque to other wavelengths in at least the visiblespectrum. The first wavelength range is other than the second wavelengthrange. In some embodiments, the first wavelength range overlaps thesecond wavelength range. In some embodiments, the first wavelength rangedoes not overlap the second wavelength range. A motor, in the interiorof the casing, is configured to move the filter housing. A circuitboard, also in the interior of the casing, comprises non-transitoryinstructions for implementing at least a portion of ahyperspectral/multispectral imaging regimen. The instructions forimplementing the hyperspectral/multispectral imaging regimen includeinstructions for driving the motor in accordance with thehyperspectral/multispectral imaging regimen. The attachment devicefurther includes a communications interface, configured to sendinstructions to an external device. The external device comprises atwo-dimensional imager and a light source. The instructions sent by theattachment device control the two-dimensional imager and the lightsource in accordance with the hyperspectral/multispectral imagingregimen. The attachment device is attached to the external device. Theattachment device further includes a source of power, in the interior ofthe casing, to power the circuit board, the motor, and thecommunications interface.

In some embodiments, the second optical window or the fourth opticalwindow comprises a first light source polarizer that polarizes light inthe second optical path. In some embodiments, the second optical windowor the fourth optical window comprises a first homogenizer thathomogenizes light in the second optical path.

In some embodiments, the two-dimensional imager of the external deviceis a charge-coupled device (CCD), a complementarymetal-oxide-semiconductor (CMOS), a photo-cell, or a focal plane array.

In some embodiments, the plurality of filters comprises at least onebandpass filter. In some embodiments, the plurality of filters comprisesat least one longpass filter or at least one shortpass filter.

In some embodiments, the hyperspectral/multispectral imaging regimencomprises instructions for driving the filter housing to a firstposition in which the first filter selectively intercepts the firstoptical path. The hyperspectral/multispectral imaging regimen furthercomprises instructions for communicating instructions, via thecommunications interface, to the light source to power on. Thehyperspectral/multispectral imaging regimen further comprisesinstructions for communicating instructions, via the communicationsinterface, to the two-dimensional imager to acquire a first image oflight passing through the first optical path when the filter housing isin the first position. The hyperspectral/multispectral imaging regimenfurther comprises instructions for driving, after the first image isacquired, the filter housing to a second position in which the secondfilter selectively intercepts the first optical path and the firstfilter no longer intercepts the first optical path. Thehyperspectral/multispectral imaging regimen further comprisesinstructions for communicating instructions, via the communicationsinterface, to the two-dimensional imager, to acquire a second image oflight passing through the first optical path when the filter housing isin the second position.

In some embodiments, the communication interface comprises a wirelesssignal transmission element and instructions are sent in accordance withthe hyperspectral/multispectral imaging regimen to the external lightsource by the wireless signal transmission element. In some embodiments,the wireless signal transmission element is selected from the groupconsisting of a Bluetooth transmission element, a ZigBee transmissionelement, and a Wi-Fi transmission element.

In some embodiments, the communication interface comprises a firstcommunications interface and instructions are sent in accordance withthe hyperspectral/multispectral imaging regimen to the external light bya cable coupled to the first communications interface source and asecond communications interface of the external device.

In some embodiments, the communications interface comprises a firstcommunications interface and the housing attaches to the external devicethereby bringing the first communications interface in direct physicaland electrical communication with a second communications interface ofthe external device thereby enabling instructions to be sent directly tothe second communications interface from the first communicationsinterface in accordance with the hyperspectral/multispectral imagingregimen.

In some embodiments, the external device is selected from the groupconsisting of a smart phone, a personal digital assistant (PDA), anenterprise digital assistant, a tablet computer, and a digital camera.

In some embodiments, the external device further comprises a display,and the hyperspectral/multispectral imaging regimen further comprisesinstructions for displaying an image captured by the two-dimensionalimager, in accordance with the hyperspectral/multispectral imagingregimen, on the housing display. In some embodiments, the housingdisplay is a touch screen display and the displayed image is configuredto be enlarged or reduced by human touch to the touch screen display.

In some embodiments, the housing display is used for focusing an imageof a surface of a subject acquired by the two-dimensional imager.

In some embodiments, the attachment device has a maximum powerconsumption of less than 15 watts, less than 10 watts, or less than 5watts. In some embodiments, the source of power for the attachmentdevice is a battery (e.g., a rechargeable battery).

In some embodiments, the communications interface of the attachmentdevice comprises a first communications interface, and attachment of thehousing to the external device brings the first communications interfacein direct physical and electrical communication with a secondcommunications interface of the external device thereby enablinginstructions to be sent directly to the second communications interfacefrom the first communications interface in accordance with thehyperspectral/multispectral imaging regimen. In some such embodiments,the source of power is a battery and the battery is recharged throughthe first communications interface by electrical power obtained from thesecond communications interface of the external device.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 10 nm, or by atleast 25 nm.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 50 nm.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 100 nm.

In some embodiments, the first filter is a shortpass filter and thesecond filter is a longpass filter.

In some embodiments, the instructions sent via the communicationsinterface to the light source to power on instruct the light source topower on for no longer than one second, no longer than 500 milliseconds,or no longer than 250 milliseconds.

In some embodiments, the plurality of filters comprises four or morebandpass filters, with each bandpass filter in the four or more bandpassfilters characterized by a different central wavelength. In someembodiments, the plurality of filters comprises six or more bandpassfilters, with each bandpass filter in the six or more bandpass filterscharacterized by a different central wavelength. In some embodiments,the plurality of filters comprises eight or more bandpass filters, witheach bandpass filter in the eight or more bandpass filters characterizedby a different central wavelength.

In some embodiments, the first wavelength range is 40 nm or less and thesecond wavelength range is 40 nm or less. In some embodiments, the firstwavelength range is 20 nm or less and the second wavelength range is 20nm or less. In some embodiments, the first wavelength range is 10 nm orless and the second wavelength range is 10 nm or less.

In some embodiments, the non-transitory instructions for implementingthe hyperspectral/multispectral imaging regimen are stored in one ormore memory chips of the circuit board.

In some embodiments, the communications interface is configured toreceive the instructions for implementing a hyperspectral/multispectralimaging regimen from the external device and the at least portion of theregimen is stored in one or more memory chips of the circuit board.

In some embodiments, the filter housing comprises a filter wheel and themotor drives the filter wheel about the axis to thereby selectivelyintercept the first optical path with a predetermined one of the filtersin the plurality of filters.

In some embodiments, the filter housing comprises a filter strip, andthe motor drives the filter strip along the axis to thereby selectivelyintercept the first optical path with a predetermined one of the filtersin the plurality of filters.

Non-Transitory Computer Readable Storage Medium Embodiments. Anotheraspect of the present disclosure provides a non-transitory computerreadable storage medium comprising instructions for execution by one ormore processors to perform a hyperspectral/multispectral imaging regimencomprising providing motor step function instructions that instruct amotor to move a filter housing in a casing to a first position. Thefilter housing comprises a plurality of filters. The first positioncauses a first filter in the plurality of filters to selectivelyintercept a first optical path through a casing housing the plurality offilters. The first filter is transparent to a first wavelength range andopaque to other wavelengths in at least the visible spectrum. Thehyperspectral/multispectral imaging regimen further comprisesinstructing a light source to power on and subsequently or concurrentlyinstructing a two-dimensional imager to acquire a first image of lightpassing through the first optical path when the filter housing is in thefirst position. the hyperspectral/multispectral imaging regimen furthercomprises providing motor step function instructions that instruct themotor to move the filter wheel to a second position, after the firstimage is acquired. The second position causes a second filter in theplurality of filters to selectively intercept the first optical path(and causes the first filter to no longer intercept the first opticalpath). The second filter is transparent to a second wavelength range andopaque to other wavelengths in at least the visible spectrum. The firstwavelength range is other than the second wavelength range. Thehyperspectral/multispectral imaging regimen instructs thetwo-dimensional imager to acquire a second image of light passingthrough the first optical path when the filter wheel is in the secondposition. The hyperspectral/multispectral imaging regimen combines atleast the first image and the second image to form ahyperspectral/multispectral image.

In some embodiments, the two-dimensional imager is a charge-coupleddevice (CCD), a complementary metal-oxide-semiconductor (CMOS), aphoto-cell, or a focal plane array.

In some embodiments, the plurality of filters comprises at least onebandpass filter. In some embodiments, the plurality of filters comprisesat least one longpass filter or at least one shortpass filter.

In some embodiments, the motor step functions are communicatedwirelessly in accordance with a transmission protocol (e.g., Bluetooth,ZigBee, or 802.11).

In some embodiments, the method further comprises displaying the firstimage, the second image or the hyperspectral/multispectral image.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 10 nm or by atleast 25 nm.

In some embodiments, the first filter is a shortpass filter and thesecond filter is a longpass filter.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 50 nm, or by atleast 100 nm.

In some embodiments, the instructions to power the light source oninstruct the light source to power on for no longer than one second, forno longer than 500 milliseconds, or for no longer than 250 milliseconds.

In some embodiments, the plurality of filters comprises four or morebandpass filters with each bandpass filter in the four or more bandpassfilters characterized by a different central wavelength. In someembodiments, the plurality of filters comprises six or more bandpassfilters with each bandpass filter in the six or more bandpass filterscharacterized by a different central wavelength. In some embodiments,the plurality of filters comprises eight or more bandpass filters, witheach bandpass filter in the eight or more bandpass filters characterizedby a different central wavelength.

In some embodiments, the first wavelength range is 40 nm or less and thesecond wavelength range is 40 nm or less. In some embodiments, the firstwavelength range is 20 nm or less and the second wavelength range is 20nm or less. In some embodiments, the first wavelength range is 10 nm orless and the second wavelength range is 10 nm or less.

In some embodiments, the filter housing comprises a filter wheel, andthe motor drives the filter wheel about an axis to thereby selectivelyintercept the first optical path with a predetermined one of the filtersin the plurality of filters. In alternative embodiments, the filterhousing comprises a filter strip and the motor drives the filter stripalong an axis to thereby selectively intercept the first optical pathwith a predetermined one of the filters in the plurality of filters.

Disclosed Methods. Another aspect of the present disclosure provides amethod for performing a hyperspectral/multispectral imaging regimen at adevice comprising one or more processors, memory storing one or moreprograms for execution by the one or more processors, a light source, acommunications interface, and a two-dimensional imager. The device isattached to an attachment device and the one or more programs singularlyor collectively communicate, through the communications interface, motorstep function instructions that instruct a motor of the attachmentdevice to move a filter housing of the attachment device in a casing ofthe attachment device to a first position. The filter housing comprisesa plurality of filters, the first position causes a first filter in theplurality of filters to selectively intercept a first optical paththrough the filter housing, and the first filter is transparent to afirst wavelength range and opaque to other wavelengths in at least thevisible spectrum. The one or more programs further singularly orcollectively instruct the light source to power on. The one or moreprograms further singularly or collectively instruct the two-dimensionalimager to acquire a first image of light passing through the firstoptical path when the filter wheel is in the first position. The one ormore programs further singularly or collectively communicate, throughthe communications interface, motor step function instructions thatinstruct the motor to move the filter housing to a second position,after the first image is acquired. The second position causes a secondfilter in the plurality of filters to selectively intercept the firstoptical path. The second filter is transparent to a second wavelengthrange and opaque to other wavelengths in at least the visible spectrum.The first wavelength range is other than the second wavelength range.The one or more programs further singularly or collectively instruct thetwo-dimensional imager to acquire a second image of light passingthrough the first optical path when the filter wheel is in the secondposition. The one or more programs further singularly or collectivelycombine at least the first image and the second image to form ahyperspectral/multispectral image.

In some embodiments, the two-dimensional imager is selected acharge-coupled device (CCD), a complementary metal-oxide-semiconductor(CMOS), a photo-cell, or a focal plane array. In some embodiments, theplurality of filters comprises at least one bandpass filter. In someembodiments, the plurality of filters comprises at least one longpassfilter or at least one shortpass filter.

In some embodiments, the communication interface comprises a wirelesssignal transmission element and the motor step function instructions aresent by the wireless signal transmission element. In some embodiments,the wireless signal transmission element is a Bluetooth transmissionelement, a ZigBee transmission element, or a Wi-Fi transmission element.

In some embodiments, the communications interface comprises a firstcommunications interface, and the device attaches to the attachmentdevice thereby bringing the first communications interface in directphysical and electrical communication with a second communicationsinterface of the attachment device thereby enabling instructions to besent directly to the second communications interface from the firstcommunications interface.

In some embodiments, the device is a smart phone, a personal digitalassistant (PDA), an enterprise digital assistant, a tablet computer, ora digital camera.

In some embodiments, the device further comprises a display, and device,and the one or more programs singularly or collectively direct for thedisplay of the first image, the second image, or ahyperspectral/multispectral image on the display. In some suchembodiments, the display is a touch screen display, and the displayedimage is enlargeable or reducible by human touch to the touch screendisplay. In some embodiments, the display is configured for focusing animage of a surface of a subject acquired by the two-dimensional imager.

In some embodiments, the attachment device has a maximum powerconsumption of less than 15 watts, less than 10 watts, or less than 5watts. In some embodiments, a source of power for the attachment deviceis a battery (e.g., a rechargeable battery).

In some embodiments, the communications interface comprises a firstcommunications interface, attachment of the device to the attachmentdevice brings the first communications interface in direct physical andelectrical communication with a second communications interface of theattachment device thereby enabling the motor step function instructionsto be sent directly to the second communications interface from thefirst communications interface, a source of power of the attachmentdevice is a battery, and the battery is recharged through the firstcommunications interface by electrical power obtained from the secondcommunications interface of the external device.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 10 nm or by atleast 25 nm.

In some embodiments, the first and second filters are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 50 nm or by atleast 100 nm.

In some embodiments, the first filter is a shortpass filter and thesecond filter is a longpass filter.

In some embodiments, the instructing the light source to power oninstructs the light source to power on for no longer than one second,for no longer than 500 milliseconds, or for no longer than 250milliseconds.

In some embodiments, the plurality of filters comprises four or morebandpass filters with each bandpass filter in the four or more bandpassfilters characterized by a different central wavelength. In someembodiments, the plurality of filters comprises six or more bandpassfilters with each bandpass filter in the six or more bandpass filterscharacterized by a different central wavelength. In some embodiments,the plurality of filters comprises eight or more bandpass filters witheach bandpass filter in the eight or more bandpass filters characterizedby a different central wavelength.

In some embodiments, the plurality of filters includes at least fourbandpass filters with central wavelengths selected from 520±3 nm, 540±3nm, 560±3 nm, 580±3 nm, 590±3 nm, 610±3 nm, 620±3 nm, and 660±3 nm. Insome embodiments, the plurality of filters includes at least fivebandpass filters with central wavelengths selected from 520±3 nm, 540±3nm, 560±3 nm, 580±3 nm, 590±3 nm, 610±3 nm, 620±3 nm, and 660±3 nm. Insome embodiments, the plurality of filters includes at least sixbandpass filters with central wavelengths selected from 520±3 nm, 540±3nm, 560±3 nm, 580±3 nm, 590±3 nm, 610±3 nm, 620±3 nm, and 660±3 nm. Insome embodiments, the plurality of filters includes at least sevenbandpass filters with central wavelengths selected from 520±3 nm, 540±3nm, 560±3 nm, 580±3 nm, 590±3 nm, 610±3 nm, 620±3 nm, and 660±3 nm. Insome embodiments, the plurality of filters includes at least eightbandpass filters with central wavelengths selected from 520±3 nm, 540±3nm, 560±3 nm, 580±3 nm, 590±3 nm, 610±3 nm, 620±3 nm, and 660±3 nm

In some embodiments, the first wavelength range is 40 nm or less and thesecond wavelength range is 40 nm or less. In some embodiments, the firstwavelength range is 20 nm or less and the second wavelength range is 20nm or less. In some embodiments, the first wavelength range is 10 nm orless and the second wavelength range is 10 nm or less.

In some embodiments, the filter housing comprises a filter wheel and themotor drives the filter wheel about an axis to thereby selectivelyintercept the first optical path with a predetermined one of the filtersin the plurality of filters. In alternative embodiments, the filterhousing comprises a filter strip, and the motor drives the filter stripalong an axis to thereby selectively intercept the first optical pathwith a predetermined one of the filters in the plurality of filters.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an attachment device, attached to an external device,such as a mobile device, for imaging discrete wavelength bands of aregion of interest of a subject in accordance with an embodiment of thepresent disclosure.

FIG. 2 illustrates the attachment device of FIG. 1, and how theattachment device is attached to the external device in accordance withan embodiment of the present disclosure.

FIG. 3 illustrates a filter housing that comprises a filter wheel in theattachment device of FIG. 2, in accordance with an embodiment of thepresent disclosure.

FIG. 4 provides an exploded view detailing the spatial relationshipbetween the attachment device for imaging discrete wavelength bands of aregion of interest of a subject 102, the external device, and the regionof interest of the subject, in accordance with an embodiment of thepresent disclosure.

FIG. 5 illustrates exemplary components of an external device thatattaches to an attachment device for imaging discrete wavelength bandsof a region of interest of a subject in accordance with an embodiment ofthe present disclosure.

FIG. 6 illustrates a hyperspectral data cube data store that is storedin some external devices in accordance with an embodiment of the presentdisclosure.

FIG. 7 details the spatial and logical relationship between theattachment device for imaging discrete wavelength bands of a region ofinterest of a subject and the region of interest of the subject, inaccordance with an embodiment of the present disclosure.

FIG. 8 illustrates the attachment device of FIG. 1, and how theattachment device is attached to the external device in accordance withanother embodiment of the present disclosure.

FIG. 9 illustrates a close up view of a portion of FIG. 8, illustratinga filter housing that comprises a filter strip, in accordance with anembodiment of the present disclosure.

FIG. 10 illustrates a flow chart of methods for imaging discretewavelength bands using a device in accordance with an embodiment of thepresent disclosure.

FIG. 11 illustrates a continuation of the flow chart of FIG. 10 inaccordance with an embodiment of the present disclosure.

FIG. 12 illustrates a continuation of the flow chart of FIG. 11 inaccordance with an embodiment of the present disclosure.

FIG. 13 illustrates a continuation of the flow chart of FIG. 12 inaccordance with an embodiment of the present disclosure.

FIG. 14 illustrates a distributed diagnostic environment including anattachment device, attached to an external device, for imaging discretewavelength bands of a region of interest of a subject in accordance withan embodiment of the present disclosure.

DETAILED DESCRIPTION

Introduction. Hyperspectral and multispectral imaging are relatedtechniques in larger class of spectroscopy commonly referred to asspectral imaging or spectral analysis. Typically, hyperspectral imagingrelates to the acquisition of a plurality of images, each imagerepresenting a narrow spectral band collected over a continuous spectralrange, for example, 20 spectral bands having a FWHM bandwidth of 20 nmeach, covering from 400 nm to 800 nm. In contrast, multispectral imagingrelates to the acquisition of a plurality of images, each imagerepresenting a narrow spectral band collected over a discontinuousspectral range. For the purposes of the present disclosure, the terms“hyperspectral” and “multispectral” are used interchangeably and referto a plurality of images, each image representing a narrow spectral band(having a FWHM bandwidth of between 10 nm and 30 nm, between 5 nm and 15nm, between 5 nm and 50 nm, less than 100 nm, between 1 and 100 nm,etc.), whether collected over a continuous or discontinuous spectralrange.

As used herein, the terms “narrow spectral range” or “narrowband” areused interchangeably and refer to a continuous span of wavelengths,typically consisting of a FWHM spectral band of no more than about 100nm. In certain embodiments, narrowband radiation consists of a FWHMspectral band of no more than about 75 nm, 50 nm, 40 nm, 30 nm, 25 nm,20 nm, 15 nm, 10 nm, 5 nm, 4 nm, 3 nm, 2 nm, or 1 nm.

Hyperspectral imaging involves imaging narrow spectral bands over acontinuous spectral range, and producing the spectra of all pixels inthe scene of interest. So a sensor with only 20 bands can also behyperspectral when it covers the range from 500 to 700 nm with 20 bandseach 10 nm wide. (While a sensor with 20 discrete bands covering thevisible spectrum, near-infrared, short-wavelength infrared,mid-wavelength infrared, and long-wavelength infrared would beconsidered multispectral.)

Among other aspects, the present disclosure provides methods and systemsthat enable the capture of hyperspectral/multispectral images. Thearchitecture of the disclosed hyperspectral/multispectral systemsprovided herein (e.g., attachment device), provides several advantagesover systems and methods of hyperspectral/multispectral imaging known inthe art. For example, the systems and methods provided herein allow formobile cost effective capture of images at a range of wavelengthswithout the need for a tunable filter or other conventional costlyimaging equipment. The disclosed systems and methods also enable shortersubject illumination times, shorter image exposure times, overall morerapid hyperspectral/multispectral imaging, lower power consumption, andlower manufacturing costs, to name a few benefits.

Specifically, the present application provideshyperspectral/multispectral systems and methods that make use of anattachment device comprising a cover, with first and second windows,affixed to a backing, with third and fourth windows, thereby forming acasing. The first and third windows form a first optical path with lightentering the third window passing through the first window. The secondand fourth windows form a second optical path with light entering thesecond window passing through the fourth window. A filter housing with aplurality of filters is driven by a motor so that the filters interceptthe first optical path in accordance with an imaging regimenelectronically stored in the casing interior. The imaging regimencommunicates instructions, via a communications interface of theattachment device, to an imager and light source of an external device,to which the attachment device is attached, thereby controlling thesecomponents in accordance with the regimen. As opposed to imaging systemsthat rely on line scanning to capture images at separate wavelengths(e.g., systems employing a prism or diffraction grating), the systemsdescribed herein can capture true two-dimensional co-axial images bysequentially resolving images of the object at different wavelengths bymovement of the filter housing.

Hyperspectral/multispectral systems that capture images at differentwavelengths using detectors that are slightly offset from one another(e.g., at two or more detectors positioned next to each other at the endof an optical path) require extensive computational power to index andalign the images with one another. Similarly, images captured usingimaging systems that rely on co-boring of multiple objective lenses(e.g., where the center of each objective lens points to a commontarget), must be mathematically corrected so that information obtainedfrom each objective lens transposes one-to-one. Advantageously, theimaging systems provided herein provide true co-axial aligned images,reducing the computation burden and thus increasing the speed at whichhyperspectral/multispectral data can be processed.

In one embodiment, the systems and methods provided herein are usefulfor hyperspectral/multispectral medical imaging and diagnostics. Forexample, the disclosed attachment device can be mounted on a mobilephone for easy manipulation by a healthcare professional.

In another embodiment, the systems and methods provided herein areuseful for other hyperspectral/multispectral applications such assatellite imaging (e.g., for geological sensing of minerals,agricultural imaging, and military surveillance), remote chemicalimaging, and environmental monitoring. For example, the disclosedattachment device can be mounted inside a satellite or other telescopicapparatus for remote hyperspectral/multispectral imaging.

In some embodiments, the attachment devices disclosed herein areconfigured to allow for tissue oximetry, when attached to an externaldevice. Exemplary methods for performing tissue oximetry, requiringcapture of only a limited number of images at different wavelengths, aredisclosed in U.S. patent application Ser. No. 15/267,090, the content ofwhich is expressly incorporated by reference herein, in its entirety,for all purposes.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light between about 400 nm and about 700 nm.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light between about 500 nm and about 680 nm.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light, where at least four of the narrow bands (e.g., 4, 5, 6, 7, or8 of the narrow-bands of light) have central wavelengths selected from520+3 nm, 540+3 nm, 560+3 nm, 580+3 nm, 590+3 nm, 610+3 nm, 620+3 nm,and 660+3 nm.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light, where at least four of the narrow bands (e.g., 4, 5, 6, 7, or8 of the narrow-bands of light) have central wavelengths selected from510±3 nm, 530±3 nm, 540±3 nm, 560±3 nm, 580±3 nm, 590+3 nm, 620±3 nm,and 660+3 nm.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light, where at least four of the narrow bands (e.g., 4, 5, 6, 7, or8 of the narrow-bands of light) have central wavelengths selected from520±3 nm, 540±3 nm, 560±3 nm, 580±3 nm, 590±3 nm, 610+3 nm, 620±3 nm,and 640+3 nm.

In some embodiments, the attachment devices disclosed herein areconfigured to facilitate acquisition of a set of four to twelve images(e.g., 4, 5, 6, 7, 8, 9, 10, 11, or 12 images) at different narrow-bandsof light, where at least four of the narrow bands (e.g., 4, 5, 6, 7, or8 of the narrow-bands of light) have central wavelengths selected from500±3 nm, 530±3 nm, 545±3 nm, 570±3 nm, 585±3 nm, 600±3 nm, 615±3 nm,and 640±3 nm.

In some embodiments, each narrow band of light has a full width at halfmaximum (“FWHM”) of less than 25 nm, 20 nm, 15 nm, 10 nm, or 5 nm. Insome embodiments, each narrow-band of light having a central wavelengthbelow 600 nm has a full width at half maximum of less than 20 nm, 15 nm,10 nm, or 5 nm and each narrow-band of light having a central wavelengthat or above 600 nm has a full width at half maximum of less than 25 nm,20 nm, or 15 nm (e.g., because of diminished sensitivity of photodetectors above 600 nm, images collected at higher wavelengths havelarger FWHM).

Systems for Hyperspectral/Multispectral Imaging—The Attachment Device.FIG. 1 illustrates an attachment device 100 attached to an externaldevice 200 (e.g. mobile device) for imaging discrete wavelength bands ofa region of interest 104 of a subject 102 in accordance with anembodiment of the present disclosure. In some embodiments the subject ishuman. In some embodiments the region of interest is a portion of theskin of the subject. In some embodiments the region of interest is aportion of the skin of the subject. In some embodiments the region ofinterest is a portion of the epidermis of the subject. In someembodiments the region of interest is a portion of the dermis of thesubject. In some embodiments the region of interest is a region of thesubcutaneous fat of the subject. In some embodiments the region ofinterest is a first region of the epidermis and a first region of dermisof the subject that underlies the first region of the epidermis. In someembodiments, the region of interest is less than 100 square centimeters,less than 50 square centimeters, less than 25 square centimeters or lessthan 20 square centimeters.

FIG. 2 shows a schematic illustration of the internal hardware of anattachment device 100 according to some embodiments. The attachmentdevice 100 includes a cover 202 having a first optical window 218 and asecond optical window 220. The attachment device 100 further includes abacking 212 having a third optical window 226 and a fourth opticalwindow 228. The cover 202 is affixed onto the backing 212 therebyforming a casing having an interior.

The first 218 and third 226 optical windows form a first optical path230 within the casing interior, in which light entering the thirdoptical window 226 passes through the first optical window 218. Thesecond 220 and fourth 228 optical window form a second optical path 232within the casing interior, in which light entering the second opticalwindow passes 220 through the fourth optical window. In some suchembodiments light originates from light 216 of external device 200,passes through the second optical window passes 220 along the secondoptional path 232, and out fourth optical window 228. Some of this lightis reflected from the region of interest 104 of a subject and passesback through the third optical window 226, along the first optical path230 through the first optical window 218 and into an imager 214 (e.g., atwo-dimensional imager such as a charge-coupled device, a complementarymetal-oxide-semiconductor, a photo-cell, or a focal plane array). Insome embodiments, a portion of the light is reflected by the surface ofthe skin of the subject whereas a portion of the light is transmittedthrough the air-stratum corneum interface of the subject and absorbed bychromophores (e.g., melanin and hemoglobin) in the epidermis and dermisor scattered by cells or collagen fibers present throughout theepidermis and dermis. Therefore, in some embodiments, the observed skinreflectance that passes back through the third optical window 226 insome embodiments is the sum of the surface reflection, also calledFresnel reflection, and the diffuse reflectance. The latter correspondsto light that entered the tissue and reemerged out of the tissue towardthe detector. If light 216 is polarized such that the region of interest104 of the subject 102 is illuminated by polarized light, the lightreflected by the surface remains polarized. However, the reemerginglight is depolarized due to multiple scatterings in the tissue. See, forexample, Yudovsky et al, 2010, J. Diabetes Sci Technolol. 1099-1113,which is hereby incorporated by reference in its entirety.

As disclosed in FIG. 2, attachment device 100 includes a filter housing204 in the interior of the casing. FIG. 3 illustrates an enlarged viewof the filter housing 204 in accordance with the embodiment of FIG. 2.As illustrated in FIG. 3, the filter housing 204 comprises a filterwheel which, in turn, comprises a plurality of filters 304. Each filterin the plurality of filters is characterized by a wavelength range in aplurality of wavelength ranges. The filter housing is movable about axis302 to thereby selectively intercept the first optical path 230. A firstfilter 304-1 in the plurality of filters 304 is characterized by a firstwavelength range in the plurality of wavelength ranges such that thefirst filter 304-1 is transparent to the first wavelength range andopaque to other wavelengths in at least the visible spectrum.Accordingly, in some embodiments, the filter housing 204 comprises afilter wheel and a motor 206 drives the filter wheel about an axis 304to thereby selectively intercept the first optical path 230 with apredetermined one of the filters 304 in the plurality of filters.

A second filter 304-2 in the plurality of filters 304 is characterizedby a second wavelength range in the plurality of wavelength ranges, suchthat the second filter 304-2 is transparent to the second wavelengthrange and opaque to other wavelengths in at least the visible spectrum.Furthermore, the first wavelength range 304-1 is other than the secondwavelength range 304-2. In some embodiments the first wavelength range304-1 overlaps the second wavelength range 304-2. In some embodimentsthe first wavelength range 304-1 does not overlap the second wavelengthrange 304-2. In some the first wavelength range is 40 nm or less and thesecond wavelength range is 40 nm or less. In some the first wavelengthrange is 20 nm or less and the second wavelength range is 20 nm or less.In some the first wavelength range is 10 nm or less and the secondwavelength range is 10 nm or less.

In some embodiments, the plurality of filters 304 comprises at least onebandpass filter. In some embodiments, the plurality of filters 304comprises at least one longpass filter and/or at least one shortpassfilter. In some embodiments the first 304-1 and second 304-2 filters arecharacterized by corresponding first and second central wavelengths, andthe first and second central wavelengths are separated by at least 10nm, at least 25 nm, at least 50 nm, or at least 100 nm. In someembodiments, the first filter 304-1 is a shortpass filter and the secondfilter 304-2 is a longpass filter. In some embodiments, the plurality offilters comprises four or more bandpass filters and each bandpass filterin the four or more bandpass filters is characterized by a differentcentral wavelength. In some embodiments, the plurality of filterscomprises six or more bandpass filters and each bandpass filter in thesix or more bandpass filters is characterized by a different centralwavelength. In some embodiments, the plurality of filters compriseseight or more bandpass filters and each bandpass filter in the eight ormore bandpass filters is characterized by a different centralwavelength.

As disclosed in FIG. 2, attachment device 100 includes a motor 206 inthe interior of the casing. The motor 206 is configured to move thefilter housing 204 in accordance with a hyperspectral/multispectralimaging regimen. For instance, an exemplary hyperspectral/multispectralimaging regimen comprises instructions for 8. The attachment device ofany one of claims 1-7, wherein the hyperspectral/multispectral imagingregimen comprises instructions for driving the filter housing to a firstposition in which the first filter 304-1 selectively intercepts thefirst optical path 230, communicating instructions, via a communicationsinterface (not shown), to the light source 216 of the external device200 to power on, communicating instructions, via the communicationsinterface, to the imager 214 of the external device 200 to acquire afirst image of light passing through the first optical path 230 when thefilter housing 204 is in the first position, driving, after the firstimage is acquired, the filter housing 204 to a second position in whichthe second filter 304-2 selectively intercepts the first optical path230 and the first filter 304-1 no longer intercepts the first opticalpath and communicating instructions, via the communications interface,to the two-dimensional imager 214, to acquire a second image of lightpassing through the first optical path when the filter housing 204 is inthe second position. This process continues until all the filter 304called for by the regimen have been used to capture an image. The imagesare then combined in accordance with the regimen. In some embodiments,the regimen calls for the use of all of the filters, meaning that animage is taken using each and every filter in the plurality of filterson the filter housing 204. In some embodiments, the regimen calls forthe use of only some of the filters, meaning that an image is takenusing each and every filter in a subset of the plurality of filters onthe filter housing 204.

As disclosed in FIG. 2, attachment device 100 includes a circuit board208 in the interior of the casing. The circuit board comprisesnon-transitory instructions for implementing at least a portion of ahyperspectral/multispectral imaging regimen such as the exemplaryregimen disclosed above. As such, the instructions for implementing thehyperspectral/multispectral imaging regimen include instructions fordriving the motor in accordance with the hyperspectral/multispectralimaging regimen.

Attachment device 100 further includes a communications interface,typically in the form of one or more circuits on the circuit board 208.The communications interface is configured to send instructions to theexternal device 200, in particular the imager 214 and the light source216, to control the imager and the light source in accordance with thehyperspectral/multispectral imaging regimen, for instance in the mannerdescribed above in the exemplary hyperspectral/multispectral imagingregimen.

As disclosed in FIG. 2, the attachment device 100 is attached (e.g.,reversibly attached) to the external device 200. In some embodiments,for example, the casing of the attachment device 100 is molded so thatit exactly snaps onto the external device 200. In some embodiments theattachment device 100 is adhered to the external device 200 (e.g., usingdouble sided adhesive tape or the like). In some embodiments, theexternal device is a smart phone, a personal digital assistant (PDA), anenterprise digital assistant, a tablet computer, or a digital camera.

In some embodiments, the attachment device 100 further includes a sourceof power 210 in the interior of the casing that powers the circuit board208, the motor 206, and the communications interface (not explicitlyshown). In some embodiment the source of power 210 is a battery (e.g., arechargeable battery). In some embodiments, power 210 optionallyincludes a power management system, one or more power sources (e.g.,battery, alternating current (AC)), a recharging system, a power failuredetection circuit, a power converter or inverter, a power statusindicator (e.g., a light-emitting diode (LED)) and/or any othercomponents associated with the generation, management and distributionof power in portable devices.

Advantageously, the attachment device 100 has low power consumptionrequirements in some embodiments. For instance, in some embodiments, theattachment device 100 has a total maximum power consumption of less than15 watts, less than 10 watts or less than 5 watts. In some embodiments,the attachment device 100 has a total maximum power consumption ofbetween 10 and 15 watts, between 5 and 10 watts, or between 2 and 5watts.

Turning to FIG. 4, there is disclosed an exploded view detailing thespatial relationship between the attachment device 100 for imagingdiscrete wavelength bands of a region of interest of a subject, theexternal device 200, and the region of interest 104 of the subject 102in accordance with an embodiment of the present disclosure. As disclosedin FIG. 4, light (e.g., reflected light) from the subject passes throughthe third optical window 226 of the attachment device 100, traverses thefirst optical path 230 thereby passing through a filter 304 of thefilter housing 204, passes through the first optical window 218 of theattachment device 100, to the imager 214 of the external device 200.Subsequently, in accordance with the hyperspectral/multispectral imagingregimen, the filter housing 204 is moved thereby positioning a differentfilter 304 of the filter housing in the first optical path 230 and asubsequent image of the region of interest is taken with the new filterin position. This process repeats itself until an image has been takenusing each filter 304 of the filter housing 204 specified by thehyperspectral/multispectral imaging regimen.

FIG. 8 illustrates an attachment device 100 in accordance with anotherembodiment of the present disclosure. All elements with like referencenumerals to those found in FIG. 2 are not repeated here for the sake ofbrevity. What differs between the embodiments of the attachment device100 of FIGS. 2 and 8 is that the filter housing (filter wheel) 204 ofthe attachment device of FIG. 2 is functionally replaced with the filterstrip in FIG. 8. The filter strip is moved in accordance with thehyperspectral/multispectral imaging regimens in the same manner asdisclosed above. Accordingly, and further referring to FIG. 9 whichillustrates a close up view of a portion of FIG. 8, in the embodiment ofthe attachment device 100 of FIGS. 8 and 9, the motor 206 drives thefilter strip 804 along the axis 806 to thereby selectively intercept thefirst optical path 230 with a predetermined one of the filters 304 inthe plurality of filters. In particular, in the embodiment illustrate inFIG. 8, motor 206 engages gears 850-1 and 850-2 to move along respectivetracks 852-1 and 852-2 causing the filter strip 804 to linearly move.However, one of skill in the art will appreciate that there are anynumber of ways in which the motor 206 can be configured to cause thefilter strip 804 to move in a linear direction. In fact, in someembodiments, rather than using a motor on filter strip 804 the strip ismoved into different positions by other movement mechanism, such as bysolenoid action and the like. Accordingly, in some embodiments, thedisclosed motor step function instructions are in fact instructions forsuch other movement mechanism. For instance, in the case where themovement is by solenoid, the disclosed motor step function instructionsare instructions to move the filter housing by solenoid action. Althoughthe axis 806 and the filter strip are shown as being along a longdimension of the attachment device 100, in fact, the present disclosureis not so limited. In some embodiments, the filter strip 804 is in factorthogonal to the direction disclosed in FIGS. 8 and 9. In someembodiments, the filter strip 804 is in fact juxtaposed at any anglerelative to the axis 806 of FIG. 9 such as a diagonal orientation. Insome embodiments the filter strip 804 is forced to protrude from thecasing of the attachment device 100 when in some positions.

Systems for Hyperspectral/Multispectral Imaging—The External Device.FIG. 5 schematically illustrates an exemplary external device 200 inaccordance with some embodiments of the present disclosure. In someembodiments exemplary external device 200 is a smart phone (e.g., aniPHONE), a personal digital assistant (PDA), an enterprise digitalassistant, a tablet computer, or a digital camera. In some embodiments,external device 200 is not mobile. In some embodiments, external device200 is mobile but is stabilized by a tripod. In some embodiments,external device 200 is mobile.

External device 200 has one or more processing units (CPU's) 536,peripherals interface 5632, memory controller 530, a network or othercommunications interface 546 for communication with a network 532, amemory 528 (e.g., random access memory), a user interface 540, the userinterface 540 including a display 542 and input 544 (e.g., keyboard,keypad, touch screen), an optional accelerometer 550, optional audiocircuitry 556, an optional speaker 558, an optional microphone 560, oneor more optional intensity sensors 548 for detecting intensity ofcontacts on the external device 200 (e.g., a touch-sensitive surfacesuch as a touch-sensitive display system 542 of the external device200), optional input/output (I/O) subsystem 564, an imager 214, a lightsystem (e.g., light) 216, one or more communication busses 534 forinterconnecting the aforementioned components, and a power system 538for powering the aforementioned components.

In some embodiments, the input 544 is a touch-sensitive display, such asa touch-sensitive surface. In some embodiments, the user interface 540includes one or more soft keyboard embodiments. The soft keyboardembodiments may include standard (QWERTY) and/or non-standardconfigurations of symbols on the displayed icons.

The external device 200 optionally includes, in addition toaccelerometer(s) 550, a magnetometer (not shown) and/or a GPS 552 (orGLONASS or other global navigation system) receiver for obtaininginformation concerning the location and orientation (e.g., portrait orlandscape) of the external device 200.

It should be appreciated that the external device 200 illustrated inFIG. 5 is only one example of a multifunction device, and that theexternal device 200 optionally has more or fewer components than shown,optionally combines two or more components, or optionally has adifferent configuration or arrangement of the components. The variouscomponents shown in FIG. 5 are implemented in hardware, software,firmware, or a combination thereof, including one or more signalprocessing and/or application specific integrated circuits.

Memory 528 optionally includes high-speed random access memory andoptionally also includes non-volatile memory, such as one or moremagnetic disk storage devices, flash memory devices, or othernon-volatile solid-state memory devices. Access to memory 528 by othercomponents of the external device 200, such as CPU(s) 536 is,optionally, controlled by memory controller 530.

Peripherals interface 562 can be used to couple input and outputperipherals of the device, such as attachment device 100, to CPU(s) 536and memory 528. The one or more processors 536 run or execute varioussoftware programs and/or sets of instructions stored in memory 528 toperform various functions for the external device 200 and to processdata.

In some embodiments, the peripherals interface 562, CPU(s) 536, andmemory controller 530 are, optionally, implemented on a single chip. Insome other embodiments, they are, optionally, implemented on separatechips.

In some embodiments, the RF (radio frequency) circuitry of the networkinterface 546 receives and sends RF signals, also called electromagneticsignals. The RF circuitry 546 converts electrical signals to/fromelectromagnetic signals and communicates with communications networksand other devices, such as attachment device 100 in some embodiments,via the electromagnetic signals. The RF circuitry 546 optionallyincludes well-known circuitry for performing these functions, includingbut not limited to an antenna system, an RF transceiver, one or moreamplifiers, a tuner, one or more oscillators, a digital signalprocessor, a CODEC chipset, a subscriber identity module (SIM) card,memory, and so forth. RF circuitry 546 optionally communicates withnetworks 532. In some embodiments, circuitry 546 does not include RFcircuitry and, in fact, is connected to network 532 through one or morehard wires (e.g., an optical cable, a coaxial cable, or the like).

Examples of networks 532 include, but are not limited to, the World WideWeb (WWW), an intranet and/or a wireless network, such as a cellulartelephone network, a wireless local area network (LAN) and/or ametropolitan area network (MAN), and other devices by wirelesscommunication. Another example of a network includes an 802.11 network,such as an 802.11 hotspot. The wireless communication optionally usesany of a plurality of communications standards, protocols andtechnologies, including but not limited to Global System for MobileCommunications (GSM), Enhanced Data GSM Environment (EDGE), high-speeddownlink packet access (HSDPA), high-speed uplink packet access (HSDPA),Evolution, Data-Only (EV-DO), HSPA, HSPA+, Dual-Cell HSPA (DC-HSPDA),long term evolution (LTE), near field communication (NFC), wideband codedivision multiple access (W-CDMA), code division multiple access (CDMA),time division multiple access (TDMA), Bluetooth, Wireless Fidelity(Wi-Fi) (e.g., IEEE 802.11a, IEEE 802.11ac, IEEE 802.11ax, IEEE 802.11b,IEEE 802.11g and/or IEEE 802.11n), voice over Internet Protocol (VoIP),Wi-MAX, a protocol for e mail (e.g., Internet message access protocol(IMAP) and/or post office protocol (POP)), instant messaging (e.g.,extensible messaging and presence protocol (XMPP), Session InitiationProtocol for Instant Messaging and Presence Leveraging Extensions(SIMPLE), Instant Messaging and Presence Service (IMPS)), and/or ShortMessage Service (SMS), or any other suitable communication protocol,including communication protocols not yet developed as of the filingdate of the present disclosure.

In some embodiments, the audio circuitry 556, speaker 558, andmicrophone 560 provide an audio interface between a subject and externaldevice 200. The audio circuitry 556 receives audio data from peripheralsinterface 562, converts the audio data to an electrical signal, andtransmits the electrical signal to speaker 558. Speaker 558 converts theelectrical signal to human-audible sound waves. Audio circuitry 556 alsoreceives electrical signals converted by microphone 560 from soundwaves. Audio circuitry 556 converts the electrical signal to audio dataand transmits the audio data to peripherals interface 562 forprocessing. Audio data is, optionally, retrieved from and/or transmittedto memory 528 and/or RF circuitry 546 by peripherals interface 562.

In some embodiments, power system 538 optionally includes a powermanagement system, one or more power sources (e.g., battery, alternatingcurrent (AC)), a recharging system, a power failure detection circuit, apower converter or inverter, a power status indicator (e.g., alight-emitting diode (LED)) and any other components associated with thegeneration, management and distribution of power in portable devices.

As disclosed above, the external device 200 includes an imager 214. Insome embodiments, the imager 214 includes a charge-coupled device (CCD)or complementary metal-oxide semiconductor (CMOS) phototransistors.Imager 214 receives light from first optical window 218 of theattachment device 100 and converts the light to data representing animage. In conjunction with optical detector control module 512 (alsocalled a camera module), imager 214 captures images.

As illustrated in FIG. 5, the external device 200 preferably comprisesan operating system 502 that includes procedures for handling variousbasic system services. Operating system 502 (e.g., iOS, DARWIN, RTXC,LINUX, UNIX, OS X, WINDOWS, or an embedded operating system such asVxWorks) includes various software components and/or drivers forcontrolling and managing general system tasks (e.g., memory management,storage device control, power management, etc.) and facilitatescommunication between various hardware and software components.

In some embodiments, the external device 200 comprises an optionalelectronic address 504 (a mobile phone number, social media account, ore-mail address) associated with the device.

In some embodiments, the system memory 528 further includes one or moreof a file system 506 for controlling access to the various files anddata structures described herein, an illumination software controlmodule 508 for controlling the light source(s) described herein, afilter housing control module 510 for controlling the position of thefilter housing 204, an optical detector software control module 512 forcontrolling the imager 214 and reading digital images acquired thereby,a digital image data store 518 for storing digital images acquired bythe imager 214, a data processing software module 514 for manipulatingan acquired image or set of images, and a hyperspectral/multispectraldata cube data store 520 for storing hyperspectral/multispectral datacubes assembled from a plurality of hyperspectral/multispectral dataplanes (images), and a communication interface software control module516 for controlling the communication interface (network interfaceincluding optional RF circuitry) 546 that connects to another device(e.g., a handheld device, laptop computer, or desktop computer) and/orcommunication network 532 (e.g., a wide area network such as theInternet).

FIG. 6 illustrates with more particularity thehyperspectral/multispectral data cubes that are built, in someembodiments, from filter images acquired by imager 214 in accordancewith a hyperspectral/multispectral imaging regimen. In some embodiments,the hyperspectral/multispectral imaging regimen specifies how many stillimages are to be acquired using imager 214 of the same region ofinterest 104 of a subject and which filters 304 are to be used whentaking these images. Moreover, in some embodiments, thehyperspectral/multispectral imaging regimen specifies a length ofexposure for each such image. As illustrated in FIG. 6, thehyperspectral data cube data store 520 stores one or more hyperspectraldata cubes 606, with each such data cube 606 comprising a plurality ofdata planes (images) 608. Each respective data plane (e.g., still image)is acquired at a unique wavelength range that corresponds to the filter304 in the position of the first optical path 230 in the attachmentdevice 100 when the image for the respective data plane was acquired bythe imager 214. In some embodiments a data cube 606 comprises 4 suchdata planes 608, 5 such data planes 608, 6 such data planes 608, 7 suchdata planes 608, 8 such data planes 608, 9 such data planes 608, 10 suchdata planes 608, 11 such data planes 608, or 12 such data planes 608. Insome embodiments, each such data plane 608 has a unique wavelengthrange. In some embodiments, each such data plane 608 has a FWHMbandwidth of 20 nm and the data cube 606 collectively covers from 400 nmto 800 nm. In some embodiments, each such data plane 608 represents anarrow spectral band collected over a discontinuous spectral range. Insome embodiments, each such data plane 608 has a narrow spectral band(having a FWHM bandwidth of between 10 nm and 30 nm, between 5 nm and 15nm, between 5 nm and 50 nm, less than 100 nm, between 1 and 100 nm,etc.), whether collected over a continuous or discontinuous spectralrange.

In some embodiments, with reference to FIGS. 2, 5, 6, and 8, one or moresoftware modules installed in memory 528 of the external deviceindividually or collectively perform a hyperspectral/multispectralimaging regimen comprising in which motor step function instructionsthat instruct the motor 206 to move a filter housing (e.g., 204) in acasing to a first position. The filter housing comprises a plurality offilters 304, the first position causes a first filter 304-1 in theplurality of filters to selectively intercept a first optical path 230through a casing housing the plurality of filters. The first filter304-1 is transparent to a first wavelength range and opaque to otherwavelengths in at least the visible spectrum. Thehyperspectral/multispectral imaging regimen further instructs the lightsource 216 to power on. The hyperspectral/multispectral imaging regimenfurther instructs the imager 214 to acquire a first image 608-1-1 oflight passing through the first optical path 230 when the filter housingis in the first position. The hyperspectral/multispectral imagingregimen further provides motor step function instructions that instructthe motor 206 to move the filter wheel 204/804 to a second position,after the first image 608-1-1 is acquired. The second position causes asecond filter 304-2 in the plurality of filters 304 to selectivelyintercept the first optical path 230. The second filter 304-2 istransparent to a second wavelength range and opaque to other wavelengthsin at least the visible spectrum. The first wavelength range is otherthan the second wavelength range. The hyperspectral/multispectralimaging regimen further instructs the imager 214 to acquire a secondimage 608-1-2 of light passing through the first optical path 230 whenthe filter housing 304 is in the second position. In some embodiments,the hyperspectral/multispectral imaging regimen further instructs thefilter housing 304 to move to other positions and for other images 608at other wavelengths to be acquired. In some embodiments, thehyperspectral/multispectral imaging regimen combines at least the firstimage 608-1-1 and the second image 608-1-2 to form ahyperspectral/multispectral image 606-1.

In some embodiments, the plurality of filters 304 comprises at least onebandpass filter. In some embodiments, the plurality of filters comprisesat least one longpass filter or at least one shortpass filter. In someembodiments, the motor step functions are communicated wirelessly inaccordance with a transmission protocol (e.g., Bluetooth, ZigBee, or802.11). For instance, in some embodiments the motor step functions arecommunicated from the external device 200 to the attachment device 100using the network interface 546.

In some embodiments, the hyperspectral/multispectral imaging regimenfurther comprises displaying the first image 608-1-1, the second image608-1-1 or the hyperspectral/multispectral image 606, for instance on adisplay associated with the external device 200. In some embodiments,the first filter 304-1 and the second 304-2 filter are characterized bycorresponding first and second central wavelengths, and the first andsecond central wavelengths are separated by at least 10 nm or by atleast 25 nm. In some embodiments, the first filter is a shortpass filterand the second filter is a longpass filter. In some embodiments, thefirst and second filters are characterized by corresponding first andsecond central wavelengths, and the first and second central wavelengthsare separated by at least 50 nm, or by at least 100 nm.

In some embodiments, the instructions to power the light source 216 onthe external device 200 instruct the light source 216 to power on for nolonger than one second, for no longer than 500 milliseconds, or for nolonger than 250 milliseconds.

In some embodiments, the plurality of filters 304 comprises four or morebandpass filters with each bandpass filter in the four or more bandpassfilters characterized by a different central wavelength. In someembodiments, the plurality of filters 304 comprises six or more bandpassfilters with each bandpass filter in the six or more bandpass filterscharacterized by a different central wavelength. In some embodiments,the plurality of filters 304 comprises eight or more bandpass filters,with each bandpass filter in the eight or more bandpass filterscharacterized by a different central wavelength.

In some embodiments, the first wavelength range is 40 nm or less and thesecond wavelength range is 40 nm or less. In some embodiments, the firstwavelength range is 20 nm or less and the second wavelength range is 20nm or less. In some embodiments, the first wavelength range is 10 nm orless and the second wavelength range is 10 nm or less.

In some embodiments, as illustrated in FIGS. 2 and 3, the filter housing204 comprises a filter wheel, and the motor 206 drives the filter wheelabout an axis 302 (FIG. 3) to thereby selectively intercept the firstoptical path 230 with a predetermined one of the filters 304 in theplurality of filters. In alternative embodiments, referring to FIG. 8,the filter housing 804 comprises a filter strip and the motor 206 drivesthe filter strip along an axis to thereby selectively intercept thefirst optical path with a predetermined one of the filters in theplurality of filters.

FIG. 7 details the spatial and logical relationship between theattachment device 100 and the external device 200 for imaging discretewavelength bands of a region of interest 104 of a subject 102 and theregion of interest of the subject itself, in accordance with anembodiment of the present disclosure. The software modules installed inthe memory 528 of the external device 200 individually or collectivelyperform the above-described hyperspectral/multispectral imagingregimens. In the embodiment illustrated in FIG. 7, it is theillumination control module 508 that controls the light 206, the filterhousing control module 510 that sends the motor step functions (e.g., bynetwork interface 546 and/or through direct cable connection) direct thefilter housing 204 of the attachment device 100 to move into position,and the optical detector control module 512 that directs the externaldevice 200 to acquire images 608 (FIG. 6) using the imager 214 of theexternal device 200 in accordance with the hyperspectral/multispectralimaging regimen. In FIG. 7, in typical embodiments the light 216 is acomponent of the external device 200. In some embodiments, the light isintegrated into the casing of the external device 200, such as is foundin typical smart phones. In some embodiments, the light 216 is notintegrated into the casing of the external device 200. For instance, insome embodiments the light 216 is an attachment to the external device200. In some such embodiments, the light 216 may include a plurality ofwavelength specific diodes that are matched to individual filters 304,such that a diode in the plurality of diodes illuminates the region ofinterest when a corresponding filter 304 in the plurality of filters isin the first light path 230.

The acquired digital images 608 and hyperspectral/multispectral datacubes 606 can be stored in a storage module (e.g., hyperspectral datacube data store 520) in the system memory 528, and do not need to beconcurrently present, depending on which stages of the analysis the dataprocessing module 514 has performed. In fact, in some embodiments, priorto imaging a subject 102 and after communicating acquired digital images608 or processed data files thereof, the external device 200 containsneither acquired digital images 608 nor hyperspectral data cubes 606. Inother embodiments, after imaging a subject 102 and after communicatingacquired digital images 608 or processed data files thereof, theexternal device 200 retains acquired digital images 608 and/orhyperspectral data cubes 606 for a period of time (e.g., until storagespace is needed, for a predetermined amount of time, etc.).

In some embodiments, the programs or software modules identified abovecorrespond to sets of instructions for performing a function describedabove. The sets of instructions can be executed by one or moreprocessors, e.g., a CPU(s) 536. The above identified software modules orprograms (e.g., sets of instructions) need not be implemented asseparate software programs, procedures, or modules, and thus varioussubsets of these programs or modules may be combined or otherwisere-arranged in various embodiments. In some embodiments, the memory 528stores a subset of the modules and data structures identified above.Furthermore, the memory 528 may store additional modules and datastructures not described above.

The system memory 528 optionally also includes one or more of thefollowing software modules, which are not illustrated in FIG. 5: aspectral library which includes profiles for a plurality of medicalconditions, a spectral analyzer software module to compare measuredhyperspectral/multispectral data to a spectral library, control modulesfor additional sensors, information acquired by one or more additionalsensors, an image constructor software module for generating ahyperspectral/multispectral image, a hyperspectral/multispectral imageassembled based on a hyperspectral/multispectral data cube andoptionally fused with information acquired by an additional sensor, afusion software control module for integrating data acquired by anadditional sensor into a hyperspectral/multispectral data cube, and adisplay software control module for controlling a built-in display.

While examining a subject and/or viewing hyperspectral/multispectralimages of the subject, a physician can optionally provide input thatmodifies one or more parameters upon which a hyperspectral/multispectralimaging regimen is based. In some embodiments, this input is providedusing user interface 540. Among other things, the external device 200can be instructed to modify the spectral portion selected by a spectralanalyzer (e.g., to modify a threshold of analytical sensitivity) or tomodify the appearance of the image generated by an image constructor(e.g., to switch from an intensity map to a topological rendering).

Likewise, the external device 200 can be instructed to communicateinstructions to the imager 214 to modify the sensing properties (e.g.,an exposure setting, a frame rate, an integration rate). Otherparameters can also be modified. For example, the external device 200can be instructed to obtain a wide-view image of the subject forscreening purposes, or to obtain a close-in image of a particular regionof interest.

FIG. 14 is an example of a distributed diagnostic environment 1410including an attachment device 100 and the external device 200 forscreening and/or monitoring a medical condition at a location other thana traditional clinical environment (e.g., a doctor's office orhospital), in accordance with some embodiments of the presentdisclosure. In some embodiments, the distributed diagnostic environmentallows a subject 102 to screen for and/or monitor a medical condition athome, eliminating the need to visit a clinical environment. This isadvantageous because it greatly reduces the time and cost associatedwith screening and monitoring. The subject does not have to travel to aclinical environment and does not incur the costs of being attended toby a medical professional. This will improve patient compliance withassigned screening and/or monitoring regimens (e.g., for subjects atrisk for a particular medical condition). This will also facilitate morefrequent screening and/or monitoring. In this fashion, potentiallyserious medical conditions can be identified and treated earlier,improving the outcome for the subject.

In some implementations, the distributed diagnostic environment 1410includes one or more home healthcare environments 1470, one or morediagnostic environments 1420, one or more processing and/or storagecenters 1450, and a communication network 1456 that, together with oneor more Internet Service Providers 1460 and/or mobile phone operators1440, with concomitant cell towers 1442, allow communication between thehome healthcare environments 1470, the diagnostic environments, and/orthe processing/storage centers 1450.

In some embodiments, a subject 102 operates the external device 200(e.g., a personal smart phone, tablet computer, etc.) attached to anattachment device 100 to acquire a series of images of a region ofinterest 104, which are combined to form a hyperspectral/multispectralimage. The resulting hyperspectral/multispectral image of the region ofinterest is then processed to identify potential medical conditions thatmerit further investigation. When such a condition is identified, amedical professional 1422 is alerted of the potential medical condition,and can determine whether to intervene with the subject 102 for furtherdiagnostic evaluation and/or treatment.

In some embodiments, after acquiring the series of images, the externaldevice 200 transmits imaging data (e.g., a hyperspectral/multispectralimage data set) to a processing and/or storage center 1450, including aprocessing server 1452 and database 1454, which forms a processedhyperspectral image. In other embodiments, the external device 200and/or a processing device 1472 within the home healthcare environmentforms the processed hyperspectral image using thehyperspectral/multispectral image data set, and transmits the processedhyperspectral image to the processing and/or storage center 1450 and/ordirectly to a diagnostic environment 1420, where it is accessible by amedical professional 1422 via diagnostic device 1428. In someembodiments, a processed hyperspectral image stored in processing and/orstorage center 1450 is accessible to a medical professional 1422 in adiagnostic environment via communications device 1426. In yet otherembodiments, the external device 200 transmits imaging data directly tothe diagnostic environment, where it is processed by processing device1424 and accessible to a medical professional via diagnostic device1428.

In some implementations, the medical professional 1422, after reviewingthe processed hyperspectral image, and/or an indication of a medicalcondition generated from the processed hyperspectral image, contacts theindividual for further diagnostic evaluation (e.g., using a moresensitive hyperspectral/multispectral imaging device) and treatmentwithin a clinical environment (e.g., a doctor's office or hospital). Insome embodiments, the processed hyperspectral image, and/or anindication of a medical condition generated from the hyperspectralimage, is presented to the medical professional 1422 only if there is anabnormality or progression of a medical condition. As such, in someembodiments, the attachment device 100 is used in conjunction with anexternal device 200 to provide inexpensive and quick diagnosticassessments of a subject at home.

Exemplary methods. FIGS. 10 through 13 collectively illustrate a flowchart of methods for imaging discrete wavelength bands using a device inaccordance with an embodiment of the present disclosure. In theflowchart, preferred parts of the methods are shown in solid line boxeswhereas optional variants of the methods, or optional equipment used bythe methods, are shown in dashed line boxes. As such, FIGS. 10-13illustrate methods for performing a hyperspectral/multispectral imagingregimen. The methods are performed at a device (e.g., external device200) comprising one or more processors 536, memory 528 storing one ormore programs for execution by the one or more processors, a lightsource 216, a communications interface, and a two-dimensional imager(e.g., imager 214). The external device 200 is attached to an attachmentdevice 100. The one or more programs singularly or collectively executethe method (1002).

In some embodiments, the two-dimensional imager 214 is a charge-coupleddevice (CCD), a complementary metal-oxide-semiconductor (CMOS), aphoto-cell, or a focal plane array (1004). In some embodiments, theexternal device 200 is a smart phone, a personal digital assistant(PDA), an enterprise digital assistant, a tablet computer, or a digitalcamera (1006). In some embodiments, the attachment device has a maximumpower consumption of less than 15 watts, less than 10 watts, or lessthan 5 watts (1008). As such, advantageously, in some embodiments asource of power 210 for the attachment device 100 is a battery (e.g., arechargeable battery) (1010).

In accordance with the method, the one or more programs singularly orcollectively communicate from the external device 200 to the attachmentdevice 100, through the communications interface, motor step functioninstructions that instruct the motor 206 of the attachment device 100 tomove a filter housing 204 (FIG. 2)/804 (FIG. 8) of the attachment devicein a casing of the attachment device to a first position. The filterhousing 204/804 comprises a plurality of filters 304. The first positionof the filter housing 204/804 causes a first filter 304-1 in theplurality of filters to selectively intercept a first optical path 230through the filter housing. The first filter 304-1 is transparent to afirst wavelength range and opaque to other wavelengths in at least thevisible spectrum (1012).

In some embodiments, the plurality of filters comprises at least onebandpass filter (1014). In some embodiments, the plurality of filterscomprises at least one longpass filter (1016). In some embodiments, theplurality of filters comprises at least one shortpass filter (1018). Insome embodiments, the communication interface of the external device 200comprises a wireless signal transmission element (e.g., networkinterface including RF circuitry 546 of FIG. 5) and the motor stepfunction instructions are sent by the wireless signal transmissionelement (1020). In some such embodiments, the wireless signaltransmission element is a Bluetooth transmission element, a ZigBeetransmission element, or a Wi-Fi transmission element (1022).

In some embodiments, the plurality of filters 304 comprises four or morebandpass filters, and each bandpass filter in the four or more bandpassfilters is characterized by a different central wavelength (1024). Insome embodiments, the plurality of filters 304 comprises six or morebandpass filters, and each bandpass filter in the six or more bandpassfilters is characterized by a different central wavelength (1026). Insome embodiments, the plurality of filters 304 comprises eight or morebandpass filters, and each bandpass filter in the eight or more bandpassfilters is characterized by a different central wavelength (1028).

In some embodiments, the filter housing comprises a filter wheel 204(e.g., element 204 of FIGS. 2 and 3), and the motor 206 drives thefilter wheel about an axis 302 to thereby selectively intercept thefirst optical path 230 with a predetermined one of the filters in theplurality of filters (1030). In other embodiments, the filter housingcomprises a filter strip 804 (e.g., element 804 with reference to FIGS.8 and 9), and the motor 206 drives the filter strip 804 along an axis806 to thereby selectively intercept the first optical path 230 with apredetermined one of the filters 304 in the plurality of filters (1032).

In accordance with the method, the one or more programs singularly orcollectively instruct the light source 216 to power on (1034). In someembodiments, instructing the light source to power on instructs thelight source to power on for no longer than one second, no longer than500 milliseconds, or no longer than 250 milliseconds (1036). In someembodiments (not shown in FIG. 2 or 8) the light source is in electricalcommunication with the external device 200 but is not integral to theexternal device 200. In some such embodiments the light source comprisesa plurality of LEDs, and each such LED is characterized by a wavelengthband that is similar to or identical (e.g., matched) to a correspondingfilter in the plurality of filters. Accordingly, in some suchembodiments, one or a subset of the plurality of LEDs are powered onwhen the filter 304 corresponding to the one or the subset of theplurality of LEDs is moved into the first optical path 230.

In accordance with the method, the one or more programs singularly orcollectively instruct the two-dimensional imager 214 to acquire a firstimage 608-1-1 of light passing through the first optical path 230 whenthe filter housing 204/804 is in the first position (1038). Inaccordance with the method, the one or more programs singularly orcollectively then communicate, through the communications interface,motor step function instructions that instruct the motor 206 to move thefilter housing 204/804 to a second position, after the first image608-1-1 is acquired, where the second position causes a second filter304-2 in the plurality of filters to selectively intercept the firstoptical path 320. Here, the second filter 304-2 is transparent to asecond wavelength range and opaque to other wavelengths in at least thevisible spectrum, and the first wavelength range is other than thesecond wavelength range (1040).

In some such embodiments, the communications interface comprises a firstcommunications interface, and the external device 200 attaches to theattachment device 100 thereby bringing the first communicationsinterface in direct physical and electrical communication with a secondcommunications interface of the attachment device 100 thereby enablinginstructions to be sent directly to the second communications interfacefrom the first communications interface in accordance with thecommunicating (1042).

In some such embodiments, the communications interface comprises a firstcommunications interface, and attachment of the external device 200 tothe attachment device 100 brings the first communications interface indirect physical and electrical communication with a secondcommunications interface of the attachment device thereby enabling themotor step function instructions to be sent directly to the secondcommunications interface from the first communications interface inaccordance with the communicating. Furthermore, a source of power of theattachment device 100 is a battery, and the battery is recharged throughthe first communications interface by electrical power obtained from thesecond communications interface of the external device (1044).

In accordance with the method, the one or more programs singularly orcollectively instruct the two-dimensional imager 214 to acquire a secondimage of light 608-1-2 passing through the first optical path 320 whenthe filter housing 204/804 is in the second position (1046).

In some embodiments, the first 304-1 and second filters 304-2 arecharacterized by corresponding first and second central wavelengths, andthe first and second central wavelengths are separated by at least 10 nmor at least 25 (1048). In some embodiments, the first wavelength rangeis 40 nm or less and the second wavelength range is 40 nm or less(1050). In some embodiments, the first wavelength range is 20 nm or lessand the second wavelength range is 20 nm or less (1052). In someembodiments, the first wavelength range is 10 nm or less and the secondwavelength range is 10 nm or less (1054). In some embodiments, the firstfilter is a shortpass filter and the second filter is a longpass filter(1056). In some embodiments, the first and second filters arecharacterized by corresponding first and second central wavelengths, andthe first and second central wavelengths are separated by at least 50nm, or by at least 100 nm (1058). In some embodiments, the first image608-1-2 and the second image 608-1-2 are used to form a correspondinghyperspectral data cube 606-1.

In some embodiments, the external device 200 further comprises a display1304 (e.g., see FIG. 1), and the method further comprises displaying thefirst image 608-1-1, the second image 608-1-2, or the resultinghyperspectral/multispectral image 606-1 on the display (1060). In someembodiments, the display is a touch screen display and the displayedimage is enlargeable or reducible by human touch to the touch screen(1062). In some embodiments, the display is configured for focusing animage of a surface of a subject acquired by the two-dimensional imager214 (1064).

Spectral Analyzer. In some embodiments, the memory 528 include aspectral library and spectral analyzer for comparinghyperspectral/multispectral data 608 acquired by the external device 200to known spectral patterns associated with various medical conditions.In other embodiments, analysis of the acquiredhyperspectral/multispectral data 608 is performed on another devicessuch as a handheld device, tablet computer, laptop computer, desktopcomputer, an external server, for example in a cloud computingenvironment.

In some embodiments, a spectral library includes profiles for aplurality of medical conditions, each of which contain a set of spectralcharacteristics unique to the medical condition. A spectral analyzeruses the spectral characteristics to determine the probability orlikelihood that a region of the subject corresponding to a measuredhyperspectral/multispectral data cube 608 is inflicted with the medicalcondition. In some embodiments, each profile includes additionalinformation about the condition, e.g., information about whether thecondition is malignant or benign, options for treatment, etc. In someembodiments, each profile includes biological information, e.g.,information that is used to modify the detection conditions for subjectsof different skin types. In some embodiments, the spectral library isstored in a single database. In other embodiments, such data is insteadstored in a plurality of databases that may or may not all be hosted bythe same computer, e.g., on two or more computers addressable by widearea network. In some embodiments, the spectral library iselectronically stored in a non-volatile storage unit and recalled usingmemory controller 530 when needed.

In some embodiments, a spectral analyzer analyzes a particular spectraderived from a hyperspectral/multispectral data cube 608, the spectrahaving pre-defined spectral ranges (e.g., spectral ranges specific for aparticular medical condition), by comparing the spectral characteristicsof a pre-determined medical condition to the subject's spectra withinthe defined spectral ranges. Performing such a comparison only withindefined spectral ranges can both improve the accuracy of thecharacterization and reduce the computational power needed to performsuch a characterization.

The spectral characteristics of a medical condition, such as ischemia oran ulcer, can be determined, for example, by first identifying an actualcondition of that type on another subject, for example usingconventional visual examination, and then obtaining thewavelength-dependent backscattering R_(MC)(λ) of a representative regionof the skin affected by the medical condition. The backscattering of theaffected skin R_(MC)(λ) can then be spectrally compared to thewavelength-dependent backscattering of that subject's normal skin in thesame area of the lesion, R_(NS)(λ), by normalizing the backscattering ofthe affected skin against the backscattering of normal skin as follows:R _(MC,N)(λ)=R _(MC)(λ)/R _(NS)(λ),where R_(MC,N)(λ) is the normalized backscattering of the affected skin.In other embodiments, R_(MC,N)(λ) is instead determined by taking thedifference between R_(MC)(λ) and R_(NS)(λ), or by calculatingR_(MC,N)(λ)=[R_(MC)(λ)−R_(NS)(λ)]/[R_(MC)(λ)+R_(NS)(λ)]. Other types ofnormalization are possible. Note that if there are multiplerepresentative regions of affected skin, there will be as manynormalized backscatterings of the affected skin. These normalizedbackscatterings can be averaged together, thus accounting for thenatural spectral variation among different regions of the affected skin.Note also that because of the natural variation in characteristics ofnormal skin among individuals, as well the potential variation incharacteristics of a particular type of affected skin among individuals,it can be useful to base the model of the normalized affected skinbackscattering R_(MC,N)(λ) on the average of the backscatteringsR_(MC)(λ) of many different affected skin samples of the same type, aswell as on the average of the backscatterings R_(NS)(λ) of manydifferent types of normal skin (e.g., by obtaining R_(MC,N)(λ) for manydifferent subjects having that medical condition, and averaging theresults across the different subjects).

In one embodiment, in order to determine whether the subject has thetype of medical condition characterized by R_(MC,N)(λ), the spectralanalyzer obtains the skin reflectance of each region, R_(region)(λ),from a measured hyperspectral cube 606 or data plane 608. The spectralanalyzer then normalizes the backscattering R_(region)(λ) from thatregion against the wavelength-dependent backscattering of the subject'snormal skin in the same area, R_(NS,Subject)(λ), as follows:R _(region,N)(λ)=R _(region)(λ)/R _(NS,Subject)(λ),where R_(region,N)(λ) is the normalized backscattering of the region.Other types of normalization are possible.

In some embodiments, the spectral analyzer analyzes the subjects'spectra by comparing R_(region,N)(λ) to R_(MC,N)(λ). In one simpleexample, the comparison is done by taking the ratioR_(region,N)(λ)/R_(MC,N)(λ), or the differenceR_(MC,N)(λ)−R_(region,N)(λ). The magnitude of the ratio or differenceindicates whether any region has spectral characteristics that matchthat of affected skin. However, while ratios and differences are simplecalculations, the result of such a calculation is complex and requiresfurther analysis before a diagnosis can be made. Specifically, the ratioor subtraction of two spectra, each of which has many peaks, generates acalculated spectrum that also has many peaks. Some peaks in thecalculated spectrum may be particularly strong (e.g., if the subject hasthe medical condition characterized by R_(MC,N)(λ)), but other peaks mayalso be present (e.g., due to noise, or due to some particularcharacteristic of the subject). A physician in the examination roomwould typically find significantly more utility in a simple “yes/no”answer as to whether the subject has a medical condition, than he wouldin a complex spectrum. One method of obtaining a “yes/no” answer is tocalculate whether a peak in the calculated spectrum has a magnitude thatis above or below a predetermined threshold and is present at awavelength that would be expected for that medical condition.

Another way to obtain a “yes/no” answer is to treat R_(region,N)(λ) andR_(MC,N)(λ) as vectors, and to determine the “angle” between thevectors. The angle represents the degree of overlap between the vectors,and thus represents how likely it is that the subject has the medicalcondition. If the angle is smaller than a threshold value, the subjectis deemed to have the medical condition; if the angle does not exceed athreshold value, the subject is deemed not to have the medicalcondition. Alternately, based on the value of the angle between thevectors, a probability that the subject has the medical condition can bedetermined.

In one embodiment, a spectral library may comprise a personalizeddatabase of spectral information that is collected for a particularsubject. The personalized database can then be used to monitor changesin the subject over time. Changes over time in the spectralcharacteristics of a region on the subject can be used to provideinformation, for example, on the progression or regression of a medicalcondition, the efficacy of treatment, and the appearance of a newmedical condition (e.g., the formation of an ulcer). The providedinformation can be used to inform the medical treatment of the subject.For further details, see U.S. Patent Publication No. 2009/0326383, thecontent of which is hereby incorporated herein by reference in itsentirety for all purposes.

In certain embodiments, the spectral analyzer includes a trained dataanalysis algorithm for identifying a region on the subject's skin ofbiological interest using an image obtained by the apparatus and/or fordetermining a portion of a hyperspectral/multispectral data cube thatcontains information about a biological insult in the subject's skin. Awide variety of pattern classification techniques and/or statisticaltechniques can be used in accordance with the present disclosure to helpin the analysis. For instance, such pattern classification techniquesand/or statistical techniques can be used to (i) assist in identifying amedical condition of a subject, (ii) assist in characterizing a medicalcondition of a subject, and (iii) assist in analyzing the progression ofa medical condition of a subject (e.g., detect changes in tissuecomposition or a wound on the skin of a patient over time). For furtherdetails, see U.S. Patent Publication No. 2009/0326383, the content ofwhich is hereby incorporated herein by reference in its entirety for allpurposes.

Pattern classification is used to mine a spectral library to identifyand characterize medical conditions (e.g., ischemia, an ulcer, diabetes,etc.) that are characterized by observable hyperspectral/multispectralsignatures. In some examples, the hyperspectral/multispectral signaturesare values of specific pixels in an image of a subject's skin, patternsof values of specific groups of pixels in an image of a subject's skin,values of specific measured wavelengths or any other form of observabledata that is directly present in the spectral data and/or that can bederived from the spectral data taken of a subject's skin. In someembodiments, pattern classification techniques such as artificialintelligence are used to analyze hyperspectral/multispectral data cubes,the output of other sensors or cameras, and/orhyperspectral/multispectral images themselves (which may or may not befused with other information), further details, see: U.S. PatentPublication No. 2009/0326383; National Research Council; Panel onDiscriminant Analysis Classification and Clustering, DiscriminantAnalysis and Clustering, Washington, D.C.: National Academy Press; andDudoit et al., JASA 97; 77-87 (2002), the contents of which are herebyincorporated herein by reference in their entireties, for all purposes.

Relevant algorithms for decision rules include, but are not limited to:discriminant analysis including linear, logistic, and more flexiblediscrimination techniques (see, e.g., Gnanadesikan, 1977, Methods forStatistical Data Analysis of Multivariate Observations, New York: Wiley1977; tree-based algorithms such as classification and regression trees(CART) and variants (see, e.g., Breiman, 1984, Classification andRegression Trees, Belmont, Calif.: Wadsworth International Group);generalized additive models (see, e.g., Tibshirani, 1990, GeneralizedAdditive Models, London: Chapman and Hall); neural networks (see, e.g.,Neal, 1996, Bayesian Learning for Neural Networks, New York:Springer-Verlag; and Insua, 1998, Feedforward neural networks fornonparametric regression In: Practical Nonparametric and SemiparametricBayesian Statistics, pp. 181-194, New York: Springer), the contents ofwhich are hereby incorporated herein by reference in their entireties,for all purposes. Other suitable data analysis algorithms for decisionrules include, but are not limited to, logistic regression, or anonparametric algorithm that detects differences in the distribution offeature values (e.g., a Wilcoxon Signed Rank Test (unadjusted andadjusted)).

Additional suitable data analysis algorithms are known in the art, someof which are reviewed in Hastie et al., (2001, The Elements ofStatistical Learning, Springer-Verlag, New York, Chapter 9, the contentof which is hereby incorporated herein by reference in its entirety forall purposes). Examples of data analysis algorithms include, but are notlimited to: Classification and Regression Tree (CART), Multiple AdditiveRegression Tree (MART), Prediction Analysis for Microarrays (PAM), andRandom Forest analysis. Such algorithms classify complex spectra and/orother information in order to distinguish subjects as normal or ashaving a particular medical condition. Other examples of data analysisalgorithms include, but are not limited to, ANOVA and nonparametricequivalents, linear discriminant analysis, logistic regression analysis,nearest neighbor classifier analysis, neural networks, principalcomponent analysis, quadratic discriminant analysis, regressionclassifiers and support vector machines. Such algorithms may be used toconstruct a decision rule and/or increase the speed and efficiency ofthe application of the decision rule and to avoid investigator bias, oneof ordinary skill in the art will realize that computer-based algorithmsare not required to carry out the disclosed methods.

In specific embodiments, suitable data analysis algorithms operable bythe central processing unit(s) 536 of the external device 200 describedherein, or by other devices or servers, are used, for example, to detectthe location and/or severity of diabetic foot ulcers or pressure ulcers.In some embodiments, suitable data analysis algorithms are used topredict the possible formation of diabetic foot ulcers or pressureulcers. Non-limiting examples of suitable data analysis algorithms forthese purposes are found in Yudovsky D. et al, J Diabetes Sci Technol.(2010) September 1; 4(5):1099-113; Yudovsky D. et al, J Biomed Opt.(2011) February; 16(2):026009, and Yudovsky D. et al., J Biophotonics(2011) August; 4(7-8):565-76, the contents of which are herebyincorporated herein by reference in their entireties for all purposes.

For additional information on the use of trained data analysisalgorithms for the analysis of hyperspectral/multispectral data, see,for example, U.S. Patent Publication Nos. 2009/0326383 and 2003/0215791,and U.S. Pat. Nos. 7,282,723 and 7,219,086, the contents of which arehereby incorporated herein by reference herein in their entireties forall purposes.

Display Subsystem. Referring to FIG. 1, in certain embodiments, theexternal device comprises a display 1304 which receives an image (e.g.,a color image, mono-wavelength image, or hyperspectral/multispectralimage 606) from a display control module, and displays the image.Optionally, the display subsystem also displays a legend that containsadditional information. For example, the legend can display informationindicating the probability that a region has a particular medicalcondition, a category of the condition, a probable age of the condition,the boundary of the condition, information about treatment of thecondition, information indicating possible new areas of interest forexamination, and/or information indicating possible new information thatcould be useful to obtain a diagnosis, e.g., another test or anotherspectral area that could be analyzed.

In one embodiment, as illustrated in FIG. 1, a housing display is builtinto the housing of the external device 200. In an example of such anembodiment, a video display in electronic communication with theprocessor 536 is mounted on the back-side of the external device 200 asillustrated. In a particular embodiment, the housing display 1304 is atouchscreen display that is used to manipulate the displayed imageand/or control the external device 200 and/or the attachment device 100.

In yet another embodiment, the external device 200 is configured to bein wired or wireless communication with an external display device, forexample, on a handheld device, tablet computer, laptop computer, desktopcomputer, television, IPOD, or projector unit, on which the image isdisplayed. Optionally, a user interface on the external display deviceis used to manipulate the displayed image and/or control thehyperspectral/multispectral system.

In one embodiment, an image can be displayed in real time on the display1304. The real-time image can be used, for example, to focus an image ofthe subject, to select an appropriate region of interest, and to zoomthe image of the subject in or out. In one embodiment, the real-timeimage of the subject is a color image captured by an optical detector.

In some embodiments, a hyperspectral/multispectral image 608 constructedfrom data collected by the imaging system is displayed on the display1304. Assembled hyperspectral/multispectral data (e.g., present in ahyperspectral/multispectral data cube) is used to create atwo-dimensional representation of the imaged object or subject, based onone or more parameters. An image constructor module, (e.g., stored inthe external device memory or in the attachment device 100 or otherdevice), constructs an image based on, for example, an analyzed spectra.Specifically, the image constructor creates a representation ofinformation within the spectra. In one example, the image constructorconstructs a two-dimensional intensity map in which thespatially-varying intensity of one or more particular wavelengths (orwavelength ranges) within the spectra is represented by a correspondingspatially varying intensity of a visible marker.

In certain embodiments, the image constructor fuses a hyperspectralimage 608 with information obtained from one or more additional sensors.Non-limiting examples of suitable image fusion methods include but arenot limited to, band overlay, high-pass filtering method, intensityhue-saturation, principle component analysis, and discrete wavelettransform. For further details on exemplary image fusion techniques, seeU.S. Patent Publication No. 2009/0326383, the content of which is herebyincorporated herein by reference in its entirety for all purposes.

Touchscreen Displays. In one embodiment, the display 1304 includes atouchscreen video display that can be manipulated by the user, forexample, to focus an image, zoom in or out within an image, select aregion of an image for further analysis, change the contrast of theimage, change a parameter of a hyperspectral/multispectral image (e.g.,the mode, spectral bands represented, artificial coloring, etc.).Touchscreens use various technologies to sense touch from a finger orstylus, such as resistive, capacitive, infrared, and acoustic sensors.Resistive sensors rely on touch to cause two resistive elementsoverlaying the display to contact one another completing a resistivecircuit, while capacitive sensors rely on the capacitance of a fingerchanging the capacitance detected by an array of elements overlaying thedisplay device. Infrared and acoustic touchscreens similarly rely on afinger or stylus to interrupt infrared or acoustic waves across thescreen, indicating the presence and position of a touch.

Capacitive and resistive touchscreens often use transparent conductorssuch as indium tin oxide (ITO) or transparent conductive polymers suchas PEDOT to form an array over the display image, so that the displayimage can be seen through the conductive elements used to sense touch.The size, shape, and pattern of circuitry have an effect on the accuracyof the touchscreen, as well as on the visibility of the circuitryoverlaying the display. Although a single layer of most suitableconductive elements is difficult to see when overlaying a display,multiple layers can be visible to a user, and some materials such asfine line metal elements are not transparent but rely on their smallsize to avoid being seen by users.

For additional information on the use of touchscreen displays, see, forexample, U.S. Pat. Nos. 7,190,348, 7,663,607, and 7,843,516 and U.S.Patent Publication Nos. 2008/0062139, 2009/0046070, 2011/0102361,2011/0095996, the contents of which are hereby incorporated herein byreference in their entireties for all purposes.

Additional Elements. In some embodiments, the external device 200 andcoupled attachment device 100 are mountable on a tripod or other fixedstructure. In some embodiments, the tripod is a fixed sensor tripod or afixed sensor tripod on wheels. In some embodiments, the external device200 and coupled attachment device 100 is mountable on a mobile or fixedrack. For example, in some embodiments, the external device 200 andcoupled attachment device 100 is mounted on a rack or other permanentfixture in an examination room.

Overview of Methods. In some embodiments, the disclosed external device200 and coupled attachment device 100 acquirehyperspectral/multispectral images of a subject, or region of interest(ROI) thereof, at a single time point, to evaluate the subject at thatparticular point in time. In other embodiments, multiplehyperspectral/multispectral images 606 of a subject, or ROI thereof, aretaken over a period of time, for example, separated by a minute, hour,day, week, month, year, or decade, to monitor, for example, the overallhealth of the subject, progression of a medical condition (e.g.,progression of a disease), regression of a medical condition, theefficacy of a treatment plan, or to proactively monitor the subject fora medical condition.

For example, in one embodiment, the feet of a subject diagnosed withdiabetes are periodically imaged by the hyperspectral/multispectraltechniques and the disclosed external device 200 and coupled attachmentdevice 100 described herein to monitor for initial signs of theformation of a diabetic foot ulcer, which occur in fifteen percent ofall diabetic patients (Brem and Tomic-Canic, J Clin Invest. 2007 May;117(5):1219-22). In varying embodiments, the patient's feet are imagedat least once a week, at least once a month, at least once every threemonths, at least once every six months, or at least once a year.

Application of Hyperspectral/Multi spectral Medical Imaging. In someembodiments, the present disclosure provides systems and methods forhyperspectral/multispectral medical imaging. These methods are based ondistinguishing the different interactions that occur between light atdifferent wavelengths and components of the human body, especiallycomponents located in or just under the skin. For example, it is wellknown that deoxyhemoglobin absorbs a greater amount of light at 700 nmthan does water, while water absorbs a much greater amount of light at1200 nm, as compared to deoxyhemoglobin. By measuring the absorbance ofa two-component system consisting of deoxyhemoglobin and water at 700 nmand 1200 nm, the individual contribution of deoxyhemoglobin and water tothe absorption of the system, and thus the concentrations of bothcomponents, can readily be determined. By extension, the individualcomponents of more complex systems (e.g., human skin) can be determinedby measuring the absorption of a plurality of wavelengths of lightreflected or backscattered off of the system.

The particular interactions between the various wavelengths of lightmeasured by hyperspectral/multispectral imaging and each individualcomponent of the system (e.g., skin) produceshyperspectral/multispectral signature, when the data is constructed intoa hyperspectral/multispectral data cube. Specifically, different regions(e.g., different ROI on a single subject or different ROI from differentsubjects) interact differently with the light depending on the presenceof, for example, a medical condition in the region, the physiologicalstructure of the region, and/or the presence of a chemical in theregion. For example, fat, skin, blood, and flesh all interact withvarious wavelengths of light differently from one another. Similarly, agiven type of cancerous lesion interacts with various wavelengths oflight differently from normal skin, from non-cancerous lesions, and fromother types of cancerous lesions. Likewise, a given chemical that ispresent (e.g., in the blood, or on the skin) interacts with variouswavelengths of light differently from other types of chemicals. Thus,the light obtained from each illuminated region of a subject has aspectral signature based on the characteristics of the region, whichsignature contains medical information about that region.

For example, the structure of skin, while complex, can be approximatedas two separate and structurally different layers, namely the epidermisand dermis. These two layers have very different scattering andabsorption properties due to differences of composition. The epidermisis the outer layer of skin. It has specialized cells called melanocytesthat produce melanin pigments. Light is primarily absorbed in theepidermis, while scattering in the epidermis is considered negligible.For further details, see G. H. Findlay, “Blue Skin,” British Journal ofDermatology 83(1), 127-134 (1970), the content of which is incorporatedherein by reference in its entirety for all purposes.

The dermis has a dense collection of collagen fibers and blood vessels,and its optical properties are very different from that of theepidermis. Absorption of light of a bloodless dermis is negligible.However, blood-born pigments like oxy- and deoxy-hemoglobin and waterare major absorbers of light in the dermis. Scattering by the collagenfibers and absorption due to chromophores in the dermis determine thedepth of penetration of light through skin.

Light used to illuminate the surface of a subject will penetrate intothe skin. The extent to which the light penetrates will depend upon thewavelength of the particular radiation. For example, with respect tovisible light, the longer the wavelength, the farther the light willpenetrate into the skin. For example, only about 32% of 400 nm violetlight penetrates into the dermis of human skin, while greater than 85%of 700 nm red light penetrates into the dermis or beyond (see, CapineraJ. L., Encyclopedia of Entomology, 2^(nd) Edition, Springer Science(2008) at page 2854, the content of which is hereby incorporated hereinby reference in its entirety for all purposes). For purposes of thepresent disclosure, when referring to “illuminating a tissue,”“reflecting light off of the surface,” and the like, it is meant thatradiation of a suitable wavelength for detection is backscattered from atissue of a subject, regardless of the distance into the subject thelight travels. For example, certain wavelengths of infra-red radiationpenetrate below the surface of the skin, thus illuminating the tissuebelow the surface of the subject.

Briefly, light from the illuminator(s) on the systems described hereinpenetrates the subject's superficial tissue and photons scatter in thetissue, bouncing inside the tissue many times. Some photons are absorbedby oxygenated hemoglobin molecules at a known profile across thespectrum of light. Likewise for photons absorbed by de-oxygenatedhemoglobin molecules. The images resolved by the optical detectorsconsist of the photons of light that scatter back through the skin tothe lens subsystem. In this fashion, the images represent the light thatis not absorbed by the various chromophores in the tissue or lost toscattering within the tissue. In some embodiments, light from theilluminators that does not penetrate the surface of the tissue iseliminated by use of polarizers. Likewise, some photons bounce off thesurface of the skin into air, like sunlight reflecting off a lake.

Accordingly, different wavelengths of light may be used to examinedifferent depths of a subject's skin tissue. Generally, high frequency,short-wavelength visible light is useful for investigating elementspresent in the epidermis, while lower frequency, long-wavelength visiblelight is useful for investigating both the epidermis and dermis.Furthermore, certain infra-red wavelengths are useful for investigatingthe epidermis, dermis, and subcutaneous tissues.

In the visible and near-infrared (VNIR) spectral range and at lowintensity irradiance, and when thermal effects are negligible, majorlight-tissue interactions include reflection, refraction, scattering andabsorption. For normal collimated incident radiation, the regularreflection of the skin at the air-tissue interface is typically onlyaround 4%-7% in the 250-3000 nanometer (nm) wavelength range. Forfurther details, see R. R. Anderson and J. A. Parrish, “The optics ofhuman skin,” Journal of Investigative Dermatology 77(1), 13-19 (1981),the content of which is hereby incorporated by reference in its entiretyfor all purposes. When neglecting the air-tissue interface reflectionand assuming total diffusion of incident light after the stratum corneumlayer, the steady state VNIR skin reflectance can be modeled as thelight that first survives the absorption of the epidermis, then reflectsback toward the epidermis layer due the isotropic scattering in thedermis layer, and then finally emerges out of the skin after goingthrough the epidermis layer again.

Using a two-layer optical model of skin, the overall backscattering canbe modeled as:R(λ)=T _(E) ²(λ)R _(D)(λ)where T_(E)(λ) is the transmittance of epidermis and R_(D)(λ) is thereflectance of dermis. The transmittance due to the epidermis is squaredbecause the light passes through it twice before emerging out of skin.Assuming the absorption of the epidermis is mainly due to the melaninconcentration, the transmittance of the epidermis can be modeled as:T _(E)(λ)=exp(d _(E) c _(m) m(λ))where d_(E) is the depth of the epidermis, cm is the melaninconcentration and m(λ) is the absorption coefficient function formelanin. For further details, see S. L. Jacques, “Skin optics,” OregonMedical Laser Center News Etc. (1988), the content of which is herebyincorporated herein by reference in its entirety for all purposes. Foradditional information on modeling reflectance, backscattering,transmittance, absorption, and internal scattering of skin, see, U.S.Patent Application Publication No. 2009/0326383 to Barnes et al., thecontent of which is hereby incorporated herein by reference in itsentirety for all purposes.

The value of a tissue's (e.g., skin) backscattering as a function ofwavelength, R(λ), can be used to obtain medical information about thetissue and its underlying structures. For example, when skin cancerslike basal cell carcinoma (BCC), squamous cell carcinoma (SCC), andmalignant melanoma (MM) grow in the skin, the molecular structure of theaffected skin changes. Malignant melanoma is a cancer that begins in themelanocytes present in the epidermis layer. For further details, see“Melanoma Skin Cancer,” American Cancer Society (2005), the content ofwhich is hereby incorporated herein by reference in its entirety for allpurposes. Most melanoma cells produce melanin that in turn changes thebackscattering characteristics as a function of wavelength R(λ) of theaffected skin. Squamous and basal cells are also present in theepidermis layer. The outermost layer of the epidermis is called thestratum corneum. Below it are layers of squamous cells. The lowest partof the epidermis, the basal layer, is formed by basal cells. Bothsquamous and basal cell carcinomas produce certain viral proteins thatinteract with the growth-regulating proteins of normal skin cells. Theabnormal cell growth then changes the epidermis optical scatteringcharacteristics and consequently the skin backscattering properties as afunction of wavelength R(λ). Thus, information about different skinconditions (e.g., normal skin, benign skin lesions and skin cancers) canbe obtained by characterizing the backscattering R(λ) from the tissue.

Accordingly, the systems and methods described herein can be used todiagnose and characterize a wide variety of medical conditions. In oneembodiment, the concentration of one or more skin or blood component isdetermined in order to evaluate a medical condition in a patient.Non-limiting examples of components useful for medical evaluationinclude: deoxyhemoglobin levels, oxyhemoglobin levels, total hemoglobinlevels, oxygen saturation, oxygen perfusion, hydration levels, totalhematocrit levels, melanin levels, collagen levels, and bilirubinlevels. Likewise, the pattern, gradient, or change over time of a skinor blood component can be used to provide information on the medicalcondition of the patient.

Non-limiting examples of conditions that can be evaluated byhyperspectral/multispectral imaging, include: tissue ischemia, ulcerformation, ulcer progression, venous stasis, venous ulcer disease,infection, shock, cardiac decompensation, respiratory insufficiency,hypovolemia, the progression of diabetes, congestive heart failure,sepsis, dehydration, hemorrhage, hypertension, exposure to a chemical orbiological agent, and an inflammatory response.

In one embodiment, the systems and methods described herein are used toevaluate tissue oximetry and correspondingly, medical conditionsrelating to patient health derived from oxygen measurements in thesuperficial vasculature. In certain embodiments, the systems and methodsdescribed herein allow for the measurement of oxygenated hemoglobin,deoxygenated hemoglobin, oxygen saturation, oxygen usage, and oxygenperfusion. Processing of these data provide information to assist aphysician with, for example, diagnosis, prognosis, assignment oftreatment, assignment of surgery, and the execution of surgery forconditions such as peripheral arterial disease (PAD), ulceration,gangrene, venous stasis, venous ulcer disease, infection, cardiacdecompensation, respiratory insufficiency, hypovolemia, congestive heartfailure, sepsis, dehydration, hypertension, critical limb ischemia,diabetic foot ulcers, pressure ulcers, peripheral vascular disease,surgical tissue health, etc.

In one embodiment, the systems and methods described herein are used toevaluate diabetic and pressure ulcers. Development of a diabetic footulcer is commonly a result of a break in the barrier between the dermisof the skin and the subcutaneous fat that cushions the foot duringambulation. This rupture can lead to increased pressure on the dermis,resulting in tissue ischemia and eventual death, and ultimatelymanifesting in the form of an ulcer (Frykberg R. G. et al., DiabetesCare 1998; 21(10):1714-9). Measurement of oxyhemoglobin,deoxyhemoglobin, and/or oxygen saturation levels byhyperspectral/multispectral imaging can provide medical informationregarding, for example: a likelihood of ulcer formation at an ROI,diagnosis of an ulcer, identification of boundaries for an ulcer,progression or regression of ulcer formation, a prognosis for healing ofan ulcer, the likelihood of amputation resulting from an ulcer. Furtherinformation on hyperspectral/multispectral methods for the detection andcharacterization of ulcers, e.g., diabetic foot ulcers, are found inU.S. Patent Application Publication No. 2007/0038042, and Nouvong A. etal., Diabetes Care. 2009 November; 32(11):2056-61, the contents of whichare hereby incorporated herein by reference in their entireties for allpurposes.

In one embodiment, the systems and methods described herein are used toevaluate shock in a subject. Clinical presentation of shock is variablefrom subject to subject. While common indicators for a state of shockinclude low blood pressure, decreased urine output, and confusion, thesesymptoms do not manifest in all subjects (Tintinalli J. E., “EmergencyMedicine: A Comprehensive Study Guide,” New York: McGraw-Hill Companies.pp. 165-172). However, it was found that changes in cutaneous oxygensaturation, an underlying cause of shock, present as pronouncedhyperspectral mottling patterns in subjects experiencing hemorrhagicshock (U.S. Patent Application Publication No. 2007/0024946).Accordingly, measurement of oxyhemoglobin, deoxyhemoglobin, and/oroxygen saturation levels by hyperspectral/multispectral imaging canprovide medical information regarding, for example: a likelihood of asubject entering a state of shock, diagnosis of a state of shock,progression or regression of a state of shock, and a prognosis for therecovery from a state of shock. In certain embodiments, the shock ishemorrhagic shock, hypovolemic shock, cardiogenic shock, septic shock,anaphylactic shock, or neurogenic shock. Methods for the detection andcharacterization of shock are found in U.S. Patent ApplicationPublication No. 2007/0024946, the content of which is herebyincorporated herein by reference in its entirety for all purposes.

Further examples of medical conditions that may be diagnosed and/orcharacterized by the methods and systems of the present disclosureinclude, but are not limited to: abrasion, alopecia, atrophy, avmalformation, battle sign, bullae, burrow, basal cell carcinoma, burn,candidal diaper dermatitis, cat-scratch disease, contact dermatitis,cutaneous larva migrans, cutis marmorata, dermatoma, ecchymosis,ephelides, erythema infectiosum, erythema multiforme, eschar,excoriation, fifth disease, folliculitis, graft vs. host disease,guttate, guttate psoriasis, hand, foot and mouth disease,Henoch-Schonlein purpura, herpes simplex, hives, id reaction, impetigo,insect bite, juvenile rheumatoid arthritis, Kawasaki disease, keloids,keratosis pilaris, Koebner phenomenon, Langerhans cell histiocytosis,leukemia, lichen striatus, lichenification, livedo reticularis,lymphangitis, measles, meningococcemia, molluscum contagiosum,neurofibromatosis, nevus, poison ivy dermatitis, psoriasis, scabies,scarlet fever, scar, seborrheic dermatitis, serum sickness, Shagreenplaque, Stevens-Johnson syndrome, strawberry tongue, swimmers' itch,telangiectasia, tinea capitis, tinea corporis, tuberous sclerosis,urticaria, varicella, varicella zoster, wheal, xanthoma, zosteriform,basal cell carcinoma, squamous cell carcinoma, malignant melanoma,dermatofibrosarcoma protuberans, Merkel cell carcinoma, and Kaposi'ssarcoma.

Other examples of medical conditions include, but are not limited to:tissue viability (e.g., whether tissue is dead or living, and/or whetherit is predicted to remain living); tissue ischemia; malignant cells ortissues (e.g., delineating malignant from benign tumors, dysplasias,precancerous tissue, metastasis); tissue infection and/or inflammation;and/or the presence of pathogens (e.g., bacterial or viral counts). Someembodiments include differentiating different types of tissue from eachother, for example, differentiating bone from flesh, skin, and/orvasculature. Some embodiments exclude the characterization ofvasculature.

In yet other embodiments, the systems and methods provided herein can beused during surgery, for example to determine surgical margins, evaluatethe appropriateness of surgical margins before or after a resection,evaluate or monitor tissue viability in near-real time or real-time, orto assist in image-guided surgery. For more information on the use ofhyperspectral/multispectral imaging during surgery, see, Holzer M. S. etal., J Urol. 2011 August; 186(2):400-4; Gibbs-Strauss S. L. et al., MolImaging. 2011 April; 10(2):91-101; and Panasyuk S. V. et al., CancerBiol Ther. 2007 March; 6(3):439-46, the contents of which are herebyincorporated herein by reference in their entirety for all purposes.

For more information on the use of hyperspectral/multispectral imagingin medical assessments, see, for example: Chin J. A. et al., J VascSurg. 2011 December; 54(6):1679-88; Khaodhiar L. et al., Diabetes Care2007; 30:903-910; Zuzak K. J. et al., Anal Chem. 2002 May 1;74(9):2021-8; Uhr J. W. et al., Transl Res. 2012 May; 159(5):366-75;Chin M. S. et al., J Biomed Opt. 2012 February; 17(2):026010; Liu Z. etal, Sensors (Basel). 2012; 12(1):162-74; Zuzak K. J. et al., Anal Chem.2011 Oct. 1; 83(19):7424-30; Palmer G. M. et al., J Biomed Opt. 2010November-December; 15(6):066021; Jafari-Saraf and Gordon, Ann Vasc Surg.2010 August; 24(6):741-6; Akbari H. et al., IEEE Trans Biomed Eng. 2010August; 57(8):2011-7; Akbari H. et al, Conf Proc IEEE Eng Med Biol Soc.2009: 1461-4; Akbari H. et al., Conf Proc IEEE Eng Med Biol Soc. 2008:1238-41; Chang S. K. et al., Clin Cancer Res. 2008 Jul. 1;14(13):4146-53; Siddiqi A. M. et al., Cancer. 2008 Feb. 25;114(1):13-21; Liu Z. et al., Appl Opt. 2007 Dec. 1; 46(34):8328-34; ZhiL. et al., Comput Med Imaging Graph. 2007 December; 31(8):672-8;Khaodhiar L. et al., Diabetes Care. 2007 April; 30(4):903-10; Ferris D.G. et al., J Low Genit Tract Dis. 2001 April; 5(2):65-72; Greenman R. L.et al, Lancet. 2005 Nov. 12; 366(9498):1711-7; Sorg B. S. et al, JBiomed Opt. 2005 July-August; 10(4):44004; Gillies R. et al., andDiabetes Technol Ther. 2003; 5(5):847-55, the contents of which arehereby incorporated herein by reference in their entirety for allpurposes.

Additional Embodiments

In one embodiment, the present disclosure provides ahyperspectral/multispectral imaging system for remote sensing. Forexample, the disclosed external device 200 and coupled attachment device100 can be mounted within a satellite or other airborne device. Theairborne device can then be used in, for example: geological surveying,e.g., in the mining and oil industries to search for oil seeps (EllisJ., “Searching for oil seeps and oil-impacted soil with hyperspectralimagery,” Earth Observation Magazine, January 2001) or pockets of othermineral resources; agricultural surveying, e.g., monitoring of crops oridentification of suitable soil; surveillance, e.g., in militaryreconnaissance; chemical imaging, e.g., for detecting harmful or toxicagents or chemical emissions; and environmental monitoring; e.g.,monitoring levels of chemicals in the atmosphere and sub-atmosphericregions.

Additionally, the low maximum power requirements of the disclosedexternal device 200 and coupled attachment device 100 described hereinmake these devices well suited for other portable applications. Forexample, as a handheld device used on the battlefield to quicklydetermine the status of a wounded soldier or detect the presence of achemical agent. For additional information on the use ofhyperspectral/multispectral imaging for triage or other battlefieldembodiments, see, U.S. Patent Publication No. 2007/0024946, the contentof which is hereby incorporated by reference in its entirety for allpurposes.

In another embodiment, the disclosed external device 200 and coupledattachment device 100, as described herein, can be used to detectharmful emissions, identify chemical spills, or otherwise identifyunsafe working conditions, e.g., at a factory, refinery, or chemicalplant. In certain embodiments, the disclosed external device 200 andcoupled attachment device 100 may be affixed on a wall, ceiling, post,etc., at a plant or factory to continuously monitor conditions of theatmosphere for safe working conditions.

In another embodiment, the disclosed external device 200 and coupledattachment device 100, as described herein, can be used for forensicanalysis. In some embodiments, the hyperspectral/multispectral methodsand systems provided herein can be used, for example: to determine thetime of death based on change in cellular chemistry analyzed by theimager; evaluate the proximity of a gunshot based on residue left ontarget; determine the severity of blunt trauma; determine whether oxygendeprivation occurred pre- or post-mortem; evaluate drug status; identifythe location and composition of body fluids present at a crime scene;determine if an injury is old or new; make field assessments; locateevidence and provide in-situ evaluation (e.g., the identification ofbrass casings over a large area); determine the location of man-madeobjects; evaluate machined surfaces having varying polarization andspectral responses, analyze bodily fluids spread over a large area;identify a point of impact; evaluate an entire incident scene (asopposed to sampling of individual points within the scene), identifydifferent hairs for DNA analysis; locate and separate out of hairs in acarpet; and analyze chemical residues present on a surface or subject(e.g., gun powder). For additional information on the use ofhyperspectral/multispectral imaging in forensics, see U.S. Pat. No.6,640,132 to Freeman and Hopmeier, the content of which is herebyincorporated herein by reference in its entirety for all purposes.

Aspects of the disclosed methodologies can be implemented as a computerprogram product that includes a computer program mechanism embedded in anon-transitory computer-readable storage medium. Further, any of themethods disclosed herein can be implemented in one or more computers orother forms of apparatus. Further still, any of the methods disclosedherein can be implemented in one or more computer program products. Someembodiments disclosed herein provide a computer program product thatencodes any or all of the methods disclosed herein. Such methods can bestored on a CD-ROM, DVD, magnetic disk storage product, or any othernon-transitory computer-readable data or program storage product. Suchmethods can also be embedded in permanent storage, such as ROM, one ormore programmable chips, or one or more application specific integratedcircuits (ASICs). Such permanent storage can be localized in a server,802.11 access point, 802.11 wireless bridge/station, repeater, router,handheld mobile device, laptop computer, desktop computer, or otherelectronic devices.

Some embodiments provide a computer program product that contains any orall of the program modules shown FIG. 5. These program modules can bestored on a CD-ROM, DVD, magnetic disk storage product, or any othercomputer-readable data or program storage product. The program modulescan also be embedded in permanent storage, such as ROM, one or moreprogrammable chips, or one or more application specific integratedcircuits (ASICs). Such permanent storage can be localized in a server,802.11 access point, 802.11 wireless bridge/station, repeater, router,mobile phone, or other electronic devices.

Hyperspectral Medical Imaging. Various implementations of the presentdisclosure provide for systems and methods useful forhyperspectral/multispectral medical imaging (HSMI). HSMI relies upondistinguishing the interactions that occur between light at differentwavelengths and components of the human body, especially componentslocated in or just under the skin. For example, it is well known thatdeoxyhemoglobin absorbs a greater amount of light at 700 nm than doeswater, while water absorbs a much greater amount of light at 1200 nm, ascompared to deoxyhemoglobin. By measuring the absorbance of atwo-component system consisting of deoxyhemoglobin and water at 700 nmand 1200 nm, the individual contribution of deoxyhemoglobin and water tothe absorption of the system, and thus the concentrations of bothcomponents, can readily be determined. By extension, the individualcomponents of more complex systems (e.g., human skin) can be determinedby measuring the absorption of a plurality of wavelengths of lightreflected or backscattered off of the system.

The particular interactions between the various wavelengths of lightmeasured by hyperspectral/multispectral imaging and each individualcomponent of the system (e.g., skin) produceshyperspectral/multispectral signature, when the data is constructed intoa hyperspectral/multispectral data cube. Specifically, different regions(e.g., different regions of interest or ROI on a single subject ordifferent ROIs from different subjects) interact differently with lightdepending on the presence of, e.g., a medical condition in the region,the physiological structure of the region, and/or the presence of achemical in the region. For example, fat, skin, blood, and flesh allinteract with various wavelengths of light differently from one another.A given type of cancerous lesion interacts with various wavelengths oflight differently from normal skin, from non-cancerous lesions, and fromother types of cancerous lesions. Likewise, a given chemical that ispresent (e.g., in the blood, or on the skin) interacts with variouswavelengths of light differently from other types of chemicals. Thus,the light obtained from each illuminated region of a subject has aspectral signature based on the characteristics of the region, whichsignature contains medical information about that region.

The structure of skin, while complex, can be approximated as twoseparate and structurally different layers, namely the epidermis anddermis. These two layers have very different scattering and absorptionproperties due to differences of composition. The epidermis is the outerlayer of skin. It has specialized cells called melanocytes that producemelanin pigments. Light is primarily absorbed in the epidermis, whilescattering in the epidermis is considered negligible. For furtherdetails, see G. H. Findlay, “Blue Skin,” British Journal of Dermatology83(1), 127-134 (1970), the content of which is incorporated herein byreference in its entirety for all purposes.

The dermis has a dense collection of collagen fibers and blood vessels,and its optical properties are very different from that of theepidermis. Absorption of light of a bloodless dermis is negligible.However, blood-born pigments like oxy- and deoxy-hemoglobin and waterare major absorbers of light in the dermis. Scattering by the collagenfibers and absorption due to chromophores in the dermis determine thedepth of penetration of light through skin.

Light used to illuminate the surface of a subject will penetrate intothe skin. The extent to which the light penetrates will depend upon thewavelength of the particular radiation. For example, with respect tovisible light, the longer the wavelength, the farther the light willpenetrate into the skin. For example, only about 32% of 400 nm violetlight penetrates into the dermis of human skin, while greater than 85%of 700 nm red light penetrates into the dermis or beyond (see, CapineraJ. L., “Photodynamic Action in Pest Control and Medicine”, Encyclopediaof Entomology, 2nd Edition, Springer Science, 2008, pp. 2850-2862, thecontent of which is hereby incorporated herein by reference in itsentirety for all purposes). For purposes of the present disclosure, whenreferring to “illuminating a tissue,” “reflecting light off of thesurface,” and the like, it is meant that radiation of a suitablewavelength for detection is backscattered from a tissue of a subject,regardless of the distance into the subject the light travels. Forexample, certain wavelengths of infra-red radiation penetrate below thesurface of the skin, thus illuminating the tissue below the surface ofthe subject.

Briefly, light from the illuminator(s) on the systems described hereinpenetrates the subject's superficial tissue and photons scatter in thetissue, bouncing inside the tissue many times. Some photons are absorbedby oxygenated hemoglobin molecules at a known profile across thespectrum of light. Likewise for photons absorbed by de-oxygenatedhemoglobin molecules. The images resolved by the optical detectorsconsist of the photons of light that scatter back through the skin tothe lens subsystem. In this fashion, the images represent the light thatis not absorbed by the various chromophores in the tissue or lost toscattering within the tissue. In some embodiments, light from theilluminators that does not penetrate the surface of the tissue iseliminated by use of polarizers. Likewise, some photons bounce off thesurface of the skin into air, like sunlight reflecting off a lake.

Accordingly, different wavelengths of light may be used to examinedifferent depths of a subject's skin tissue. Generally, high frequency,short-wavelength visible light is useful for investigating elementspresent in the epidermis, while lower frequency, long-wavelength visiblelight is useful for investigating both the epidermis and dermis.Furthermore, certain infra-red wavelengths are useful for investigatingthe epidermis, dermis, and subcutaneous tissues.

In the visible and near-infrared (VNIR) spectral range and at lowintensity irradiance, and when thermal effects are negligible, majorlight-tissue interactions include reflection, refraction, scattering andabsorption. For normal collimated incident radiation, the regularreflection of the skin at the air-tissue interface is typically onlyaround 4%-7% in the 250-3000 nanometer (nm) wavelength range. Forfurther details, see Anderson, R. R. et al., “The Optics of Human Skin”,Journal of Investigative Dermatology, 77, pp. 13-19, 1981, the contentof which is hereby incorporated by reference in its entirety for allpurposes. When neglecting the air-tissue interface reflection andassuming total diffusion of incident light after the stratum corneumlayer, the steady state VNIR skin reflectance can be modeled as thelight that first survives the absorption of the epidermis, then reflectsback toward the epidermis layer due the isotropic scattering in thedermis layer, and then finally emerges out of the skin after goingthrough the epidermis layer again.

Accordingly, the systems and methods described herein can be used todiagnose and characterize a wide variety of medical conditions. In oneembodiment, the concentration of one or more skin or blood component isdetermined in order to evaluate a medical condition in a patient.Non-limiting examples of components useful for medical evaluationinclude: deoxyhemoglobin levels, oxyhemoglobin levels, total hemoglobinlevels, oxygen saturation, oxygen perfusion, hydration levels, totalhematocrit levels, melanin levels, collagen levels, and bilirubinlevels. Likewise, the pattern, gradient, or change over time of a skinor blood component can be used to provide information on the medicalcondition of the patient.

Non-limiting examples of conditions that can be evaluated byhyperspectral/multispectral imaging include: tissue ischemia, ulcerformation, ulcer progression, pressure ulcer formation, pressure ulcerprogression, diabetic foot ulcer formation, diabetic foot ulcerprogression, venous stasis, venous ulcer disease, peripheral arterydisease, atherosclerosis, infection, shock, cardiac decompensation,respiratory insufficiency, hypovolemia, the progression of diabetes,congestive heart failure, sepsis, dehydration, hemorrhage, hemorrhagicshock, hypertension, cancer (e.g., detection, diagnosis, or typing oftumors or skin lesions), retinal abnormalities (e.g., diabeticretinopathy, macular degeneration, or corneal dystrophy), skin wounds,burn wounds, exposure to a chemical or biological agent, and aninflammatory response.

In various embodiments, the systems and methods described herein areused to evaluate tissue oximetery and correspondingly, medicalconditions relating to patient health derived from oxygen measurementsin the superficial vasculature. In certain embodiments, the systems andmethods described herein allow for the measurement of oxygenatedhemoglobin, deoxygenated hemoglobin, oxygen saturation, and oxygenperfusion. Processing of these data provide information to assist aphysician with, for example, diagnosis, prognosis, assignment oftreatment, assignment of surgery, and the execution of surgery forconditions such as critical limb ischemia, diabetic foot ulcers,pressure ulcers, peripheral vascular disease, surgical tissue health,etc.

In various embodiments, the systems and methods described herein areused to evaluate diabetic and pressure ulcers. Development of a diabeticfoot ulcer is commonly a result of a break in the barrier between thedermis of the skin and the subcutaneous fat that cushions the footduring ambulation. This rupture can lead to increased pressure on thedermis, resulting in tissue ischemia and eventual death, and ultimatelymanifesting in the form of an ulcer (Frykberg R. G. et al., “Role ofneuropathy and high foot pressures in diabetic foot ulceration”,Diabetes Care, 21(10), 1998: 1714-1719). Measurement of oxyhemoglobin,deoxyhemoglobin, and/or oxygen saturation levels byhyperspectral/multispectral imaging can provide medical informationregarding, for example: a likelihood of ulcer formation at an ROI,diagnosis of an ulcer, identification of boundaries for an ulcer,progression or regression of ulcer formation, a prognosis for healing ofan ulcer, the likelihood of amputation resulting from an ulcer. Furtherinformation on hyperspectral/multispectral methods for the detection andcharacterization of ulcers, e.g., diabetic foot ulcers, are found inU.S. Patent Application Publication No. 2007/0038042, and Nouvong, A. etal., “Evaluation of diabetic foot ulcer healing with hyperspectralimaging of oxyhemoglobin and deoxyhemoglobin”, Diabetes Care. 2009November; 32(11):2056-2061, the contents of which are herebyincorporated herein by reference in their entireties for all purposes.

Other examples of medical conditions include, but are not limited to:tissue viability (e.g., whether tissue is dead or living, and/or whetherit is predicted to remain living); tissue ischemia; malignant cells ortissues (e.g., delineating malignant from benign tumors, dysplasias,precancerous tissue, metastasis); tissue infection and/or inflammation;and/or the presence of pathogens (e.g., bacterial or viral counts).Various embodiments may include differentiating different types oftissue from each other, for example, differentiating bone from flesh,skin, and/or vasculature. Various embodiments may exclude thecharacterization of vasculature.

In various embodiments, the systems and methods provided herein can beused during surgery, for example to determine surgical margins, evaluatethe appropriateness of surgical margins before or after a resection,evaluate or monitor tissue viability in near-real time or real-time, orto assist in image-guided surgery. For more information on the use ofhyperspectral/multispectral imaging during surgery, see, Holzer M. S. etal., “Assessment of renal oxygenation during partial nephrectomy usinghyperspectral imaging”, J Urol. 2011 August; 186(2):400-4; Gibbs-StraussS. L. et al., “Nerve-highlighting fluorescent contrast agents forimage-guided surgery”, Mol Imaging. 2011 April; 10(2):91-101; andPanasyuk S. V. et al., “Medical hyperspectral imaging to facilitateresidual tumor identification during surgery”, Cancer Biol Ther. 2007March; 6(3):439-46, the contents of which are hereby incorporated hereinby reference in their entirety for all purposes.

For more information on the use of hyperspectral/multispectral imagingin medical assessments, see, for example: Chin J. A. et al., J VascSurg. 2011 December; 54(6):1679-88; Khaodhiar L. et al., Diabetes Care2007; 30:903-910; Zuzak K. J. et al., Anal Chem. 2002 May 1;74(9):2021-8; Uhr J. W. et al., Transl Res. 2012 May; 159(5):366-75;Chin M. S. et al., J Biomed Opt. 2012 February; 17(2):026010; Liu Z. etal., Sensors (Basel). 2012; 12(1):162-74; Zuzak K. J. et al., Anal Chem.2011 Oct. 1; 83(19):7424-30; Palmer G. M. et al., J Biomed Opt. 2010November-December; 15(6):066021; Jafari-Saraf and Gordon, Ann Vasc Surg.2010 August; 24(6):741-6; Akbari H. et al., IEEE Trans Biomed Eng. 2010August; 57(8):2011-7; Akbari H. et al., Conf Proc IEEE Eng Med Biol Soc.2009: 1461-4; Akbari H. et al., Conf Proc IEEE Eng Med Biol Soc. 2008:1238-41; Chang S. K. et al., Clin Cancer Res. 2008 Jul. 1;14(13):4146-53; Siddiqi A. M. et al., Cancer. 2008 Feb. 25;114(1):13-21; Liu Z. et al., Appl Opt. 2007 Dec. 1; 46(34):8328-34; ZhiL. et al., Comput Med Imaging Graph. 2007 December; 31(8):672-8;Khaodhiar L. et al., Diabetes Care. 2007 April; 30(4):903-10; Ferris D.G. et al., J Low Genit Tract Dis. 2001 April; 5(2):65-72; Greenman R. L.et al., Lancet. 2005 Nov. 12; 366(9498):1711-7; Sorg B. S. et al., JBiomed Opt. 2005 July-August; 10(4):44004; Gillies R. et al., andDiabetes Technol Ther. 2003; 5(5):847-55, the contents of which arehereby incorporated herein by reference in their entirety for allpurposes.

References. All references cited herein are hereby incorporated byreference herein in their entirety and for all purposes to the sameextent as if each individual publication or patent or patent applicationwas specifically and individually indicated to be incorporated byreference in its entirety for all purposes.

Many modifications and variations of this application can be madewithout departing from its spirit and scope, as will be apparent tothose skilled in the art. The specific embodiments described herein areoffered by way of example only, and the application is to be limitedonly by the terms of the appended claims, along with the full scope ofequivalents to which the claims are entitled.

What is claimed:
 1. A method for performing a hyperspectral/multispectral imaging regimen: at a device comprising one or more processors, memory storing one or more programs for execution by the one or more processors, a light source, a communications interface, and a two-dimensional imager, the device attached to an attachment device, the one or more programs singularly or collectively: a) communicate, through the communications interface, motor step function instructions that instruct a motor of the attachment device to move a filter housing of the attachment device in a casing of the attachment device to a first position, wherein the filter housing comprises a plurality of filters, the first position causes a first filter in the plurality of filters to selectively intercept a first optical path through the filter housing, and the first filter is transparent to a first wavelength range and opaque to other wavelengths in at least the visible spectrum; b) instruct the light source to power on; c) instruct the two-dimensional imager to acquire a first image of light passing through the first optical path when the filter housing is in the first position; d) communicate, through the communications interface, motor step function instructions that instruct the motor to move the filter housing to a second position, after the first image is acquired, wherein the second position causes a second filter in the plurality of filters to selectively intercept the first optical path, the second filter is transparent to a second wavelength range and opaque to other wavelengths in at least the visible spectrum, and the first wavelength range is other than the second wavelength range; e) instruct the two-dimensional imager to acquire a second image of light passing through the first optical path when the filter housing is in the second position; and f) combine at least the first image and the second image to form a hyperspectral/multispectral image.
 2. The method of claim 1, wherein the two-dimensional imager is selected from the group consisting of a charge-coupled device (CCD), a complementary metal-oxide-semiconductor (CMOS), a photo-cell, and a focal plane array.
 3. The method of claim 1, wherein the communication interface comprises a wireless signal transmission element and the motor step function instructions are sent by the wireless signal transmission element.
 4. The method of claim 1, wherein the communications interface comprises a first communications interface, and the device attaches to the attachment device thereby bringing the first communications interface in direct physical and electrical communication with a second communications interface of the attachment device thereby enabling instructions to be sent directly to the second communications interface from the first communications interface in accordance with the communicating a) and communicating d).
 5. The method of claim 1, wherein the device is selected from the group consisting of a smart phone, a personal digital assistant (PDA), an enterprise digital assistant, a tablet computer, and a digital camera.
 6. The method of claim 1, wherein the device further comprises a display, and the one or more programs singularly or collectively direct for the displaying of the first image, the second image, or a hyperspectral/multispectral image on the display.
 7. The method of claim 6, wherein the display is a touch screen display, and the displayed image is enlargeable or reducible by human touch to the touch screen display.
 8. The method of claim 6, wherein the display is configured for focusing an image of a surface of a subject acquired by the two-dimensional imager.
 9. The method of claim 1, wherein the attachment device has a maximum power consumption of less than 15 watts.
 10. The method of claim 1, wherein a source of power for the attachment device is a battery.
 11. The method of claim 1, wherein the communications interface comprises a first communications interface, attachment of the device to the attachment device brings the first communications interface in direct physical and electrical communication with a second communications interface of the attachment device thereby enabling the motor step function instructions to be sent directly to the second communications interface from the first communications interface in accordance with the communicating a) and communicating d); a source of power of the attachment device is a battery; and the battery is recharged through the first communications interface by electrical power obtained from the second communications interface of the external device.
 12. The method of claim 1, wherein the first and second filters are characterized by corresponding first and second central wavelengths, and wherein the first and second central wavelengths are separated by at least 10 nm.
 13. The method of claim 1, wherein the first filter is a shortpass filter and the second filter is a longpass filter.
 14. The method of claim 1, wherein the instructing the light source to power on b) instructs the light source to power on for no longer than 250 milliseconds.
 15. The method of claim 1, wherein the plurality of filters comprises four or more bandpass filters, and each bandpass filter in the four or more bandpass filters is characterized by a different central wavelength.
 16. The method of claim 1, wherein the plurality of filters comprises six or more bandpass filters, wherein each bandpass filter in the six or more bandpass filters is characterized by a different central wavelength.
 17. The method of claim 1, wherein the plurality of filters comprises eight or more bandpass filters, wherein each bandpass filter in the eight or more bandpass filters is characterized by a different central wavelength.
 18. The method of claim 1, wherein the first wavelength range is 10 nm or less and the second wavelength range is 10 nm or less.
 19. The method of claim 1, wherein the filter housing comprises a filter wheel, and the motor drives the filter wheel about an axis to thereby selectively intercept the first optical path with a predetermined one of the filters in the plurality of filters.
 20. The method of claim 1, wherein the filter housing comprises a filter strip, and the motor drives the filter strip along an axis to thereby selectively intercept the first optical path with a predetermined one of the filters in the plurality of filters. 